A new rapid and sensitive reversed-phase HPLC method for the routine analysis of diclofenac in human plasma is described. The method shows high selectivity, sensitivity, and reproducibility employing 4'-methoxydiclofenac as internal standard (IS) with UV-detection at 282 nm. The correlation of peak area ratios (diclofenac/IS) versus diclofenac plasma concentrations are linear between 5.0-2000 ng/ml with a detection limit of 3 ng/ml. Intra- and interday precision studies yielded coefficients of variation < 6.2% for all concentrations (range 20.0-1600 ng/ml). The method was applied for the assay of diclofenac in plasma of healthy volunteers after p.o. and rectal dosage of 50 mg diclofenac sodium and was found to be highly suitable for routine analyses.