Objective: To establish an HPLC method for the simultaneous determination of chloromycetin and metronidazole in chlortalidone and metronidazole spirits. Method:The HPLC method was performed on an NOV-pak C18 (150 mm × 4. 6 mm, 5 μm) column and the mobile phase consisted of methanol and water (75∶25). The flow rate was 1. 0 ml·ml-1, the detection wavelength was 297nm, the temperature of column was 30℃ and the sample size was 20 μl. Result: The calibration curve of metronidazole was linear within the range of 5-80μg·ml-1(r=0. 999 7), and the average recovery was 100. 83% with RSD of 1. 82%(n=6). The cal-ibration curve of chlortalidone was linear within the range of 50-800μg·ml-1(r=0.999 7), and the average recovery was 100.2%with RSD of 0. 55%(n=6). Conclusion: The method is simple, rapid, accurate and reproducible, and can be used in the quality control of chlortalidone and metronidazole spirits.