WASHINGTON (AP) _ President Reagan on Friday accepted the resignation of Francis M. Mullen, head of the Justice Department's Drug Enforcement Administration.

Mullen, 50, will leave effective March 1 to take a job in private business, agency officials said.

In his resignation letter, Mullen, who held a high-ranking FBI job before moving to the drug agency, told Reagan, ''I am grateful for having had the opportunity to serve in your administration and for your support for efforts to reduce drug abuse in our country.''

''I consider it a great honor to have been identified as a 'Reagan appointee,' and my service as administrator of DEA has been the high point of my 27-year law enforcement career.''

Noting Nancy Reagan's promotion of national drug rehabilitation work, Mullen said in the letter, ''Please thank Mrs. Reagan for her superb efforts in the areas of prevention, education and rehabilitation. Her commitment has made a difference and has been a very positive influence.''

There was no immediate word on a successor for Mullen, 50.

However Con Dougherty, a spokesman for the DEA, said Mullen's deputy, John C. Lawn, was among those ''in line'' for the job.

Dougherty said Mullen will take a job with Boardsen Associates, a private investigation and security company in Groton, Conn.

DEA spokesman Robert Feldkamp said Mullen has expressed interest in possibly seeking public office, although he did not elaborate.

Mullen's confirmation as administrator of the Drug Enforcement Administration was held up in the Senate as members of Congress questioned his handling of the FBI's role in the investigation in 1981 of Labor Secretary Raymond J. Donovan.

Mullen, who had been serving as executive assistant director for investigations at the FBI, was persuaded by agency Director William H. Webster to take over the drug enforcement agency in mid-1981. Mullen served as acting DEA administrator until his nomination was confirmed by the Senate in October 1983.