A rapid and sensitive high-performance liquid chromatographic method for the determination of diclofenac sodium in plasma has been developed. The method is specific and free of interference from metabolites and common anti-inflammatory agents. The UV detector (215 nm) response was linear over a range of 5-1000 ng/ml. Day-to-day and within-day calibration curves were reproducible. The method was validated by analysis of spiked human plasma samples, partly in a blind fashion. The accuracy and precision of the method are satisfactory over the range of 5-1000 ng/ml. The method was cross-checked with the GC method. Results show a correlation coefficient of 0.983 and a slope of 1.04. The method is suitable for the routine analysis of large numbers of plasma samples usually obtained in bioavailability and pharmacokinetic studies.