Patrick R. Tyson, who has served twice as acting director of the Occupational Safety and Health Administration, told OSHA staff members yesterday that he will leave the agency May 16 to join an Atlanta corporate law firm.

The departure of Tyson, 37, acting OSHA director since last April, comes while President Reagan's designee, John A. Pendergrass, is awaiting a Senate hearing on his nomination to head the agency.

Labor Department officials, who plan to announce Tyson's resignation today, hope Pendergrass will be confirmed by the time Tyson leaves. If not, the department will have to designate another interim director.

OSHA sources said yesterday that Tyson, a 14-year Labor Department employe, had been interested in the top job and decided to leave when he was passed over. Tyson said in an interview his decision was based on "a terrific opportunity" offered by the law firm of Constangy, Brooks & Smith in his native Atlanta.

Tyson served as deputy OSHA director between his stints as acting director, and he said he believed OSHA has made progress in improving its system of drafting new regulations and in enforcement.

Tyson succeeded former OSHA directors Thorne Auchter and Robert Rowland, who both had been heavily criticized, primarily by labor organizations that accused the Reagan administration of weakening workplace law enforcement.

"You never please everybody in this job," Tyson said, "No matter what decision you make, somebody is angry."

Pendergrass, 60, is manager of hazard awareness at the 3M Co. in Minnesota, and is former president of the American Industrial Hygiene Association.