A HPLC method for determination of indapamide in human serum with Sulfisoxazole as internal standard has been established. This method was carried out ODS column (5 microns). We used a mobile phase of acetonitrile: 0.05 mol/L sodium acetate buffer at pH 3.72 (45:55 V/V) and a flow rate of 1.2 ml/min. The procedure was as follows: Transfer 0.5 ml of patient serum add 10 microliters of the internal standard (0.2 mg/ml) and 9 ml ethyl acetate into 12 ml of glass centrifuge tube. Shake for 10 minutes and centrifuge at 3000 r/min for 10 minutes. Transfer the ethyl acetate phase into another tube and evaporate to dryness at 70 c under a nitrogen steam. Reconstitute the residue with methanol 50 microliters and inject 15 microliters into the chromatograph. This method is simple, rapid, sensitive and has a good linearity. The average recoveries of indapamide and internal standard were 99.5% and 98.5% respectively. The method was linear from 0.04 micrograms/ml to 0.5 micrograms/ml with correlation coefficient of 0.9998. The coefficient of variation was less than 4.6% within a day (n = 8) and less than 4.3% between days (n = 8) respectively.