To the plaudits of D.C. Mayor Marion Barry, Jr. and exclamations from neighborhood customers -- such as "it's so big" and "just great" -- Safeway Stores Inc. yesterday opened in Southwest Washington the largest grocery store in the eastern half of the United States.

But the expanded Safeway unit, with 48,600 square feet of selling space for food and a vastly larger offering of television sets, phonograph records and other household products, won't hold the title of largest store for long.

Safeway, the nation's biggest food chain, has launched the largest food retailing expansion program in the District's history as part of an even larger $40 million modernization and construction program throughout metropolitan Washington.

Although active in the Washington market for more than half a century, Safeway in recent years has lost a modest share of the growing metropolitan food market. Safeway and Giant Food Inc. still have a commanding position in the local market, accounting together for more than 60 percent of total food retail sales, but Giant's volume is estimated to exceed that of Safeway by a slight margin.

With the store opened yesterday -- after an investment of $2 million -- at 415 14th St. SE, Safeway now operates about 125 units in the Washington area. More important are plans announced yesterday that should place Safeway in a position to expand its business in the 1980s. The largest food store in the nation, for example, is being built for Safeway in the new Hechinger mall at 1601 Maryland Ave. NE. That store, with about 63,000 square feet, is scheduled to open next May.

And, as D.C. officials noted yesterday, one of the most significant factors in Safeway's area expansion plans is the substantial commitment to the District. Safeway already is by far the largest chain food store in business in the city, with 30 retail outlets.

Since the 1960s, a significant number of chain food store opeations have been closed in the District. Safeway, for example, had 58 D.C. units in 1969 compared with 30 today. But John Mitchell, property manager for Safeway's D.C. division, noted in an interview yesterday that when all expansion projects announced yesterday are completed, his company will be operating the same amount of retail square footage as it did with more stores in 1969.

Division Manager Donald J. Smith emphasized that much smaller and older stores, such as one on 7th Street a half-mile away from the new store, cannot be operated profitably in the recent environment of spiraling inflation. cLarger stores, with more parking area and ample space for more merchandise, attract a volume of business necessary for profitability, he added.

Safeway's expansion plan covers all areas of the District as well as many suburban neighborhoods, and some of the new or expanded stores already are open.

Company officials also revealed yesterday that they are looking at additional D.C. sites not included in the formal expansion plans. Specifically, the firm is considering land near the intersections of Southern Avenue and South Capitol Street, Benning Road and East Capitol Street, and Rhode Island and South Dakota avenues -- all in areas where residents have complained about the absence of food stores.

In addition to dignitaries such as Barry and D.c. Council member Nadine Winter at yesterday's opening, nearby residents were lined up well before the formal 10 a.m. ribbon-cutting. Dianne Sullivan and four other adult leaders from the Watkins Potomac Day Care Center at 12th and E streets SE, shepherded 31 youngsters through the new store, stopping to study the broad array of fruits and vegetables and other products. The trip fit in well with the children's studies of nutrition and Thanksgiving, Sullivan said.

Elease Postell, another leader of the day care group who lives across the street from the modern store, said it isa welcome addition. And Grace Thomas, a neighborhood resident for 18 years who lives at 1941 Bennet Place NE, said the addition of more merchandise to the Safeway's shelves "will be of great convenience to me -- I won't have to go to so many stores."

Safeway's 1980-1983 expansion plans for D.C. announced yesterday included projects that will cost about $20 million, add more than $240,000 of real estate tax revenues to the city and provide 222 new jobs. In the Maryland suburbs, Safeway plans to spend $12.8 million on stores that will add $174,000 of real estate tax revenues and 265 jobs; the Virginia expansions will cost $9 million, add $56,000 to real estate tax revenues and create 143 jobs.

Safeway's D.C. projects include major expansions and modernization of stores at 1701 Corcoran St. NW, 4820 42d St. NW, 1747 Columbia Rd. NW, 3830 Georgia Ave. NW, 1825 Michigan Ave. NE and 6501 Georgia Ave. NW. The supermarket at 2626 Naylor Rd. SE will get a $482,000 facelift but will not be expanded.

In Maryland, Safeway is building a 57,000-square-foot store in Greenbelt to open in January as the second-biggest supermarket now planned, while a store is being built to replace a smaller one demolished earlier this year at 923 Thayer Ave., Silver Sring; and stores are being expanded at 3500 Hamiliton St., Hyattsville, and 1101 University Blvd., Langley Park.

Virginia expansion includes a new store in Burke opened recently and an addition of 18,000 square feet to the store at 3526 King St., Alexandria, in 1981.