OBJECTIVE: To establish a HPLC method for simultaneous determination of metronidazole and chloram. phcnicol in comedo cream. METHODS: The method included a Diamonsil C18 column (250mm ? 4.6mm, 5?m) and methanol water(50 : 50,v/v)as the mobile phase and an ultraviolet detecting wavelength of 280nm .RESULTS:The calibralion curve was linear in a concentration range of ( 10 - 250)?g/ml of both metronidazole and chloramphenicol (r = 0.9 998) .The average recoveries of metronidazole and chloramphenicol were 100.53% , 100.53% and RSD were 0.79% , 0.56% respectively .CONCLUSION:The method for the determination of metronidazole and chloramphenicol was rapid and convenient. It can be used for the quality control of metronidazole and chloramphenicol in cream.