Abstract: A RP-HPLC method was developed with solid-liquid extraction technique. Plasma sample was extracted on a macroreticular resin cartridge with methanol—glacial acetic acid (99∶1) as elution solvent. After extraction, the assay was carried out on a Spherisorb C₁₈ column with p-phenylphenol as internal standard. The mobile phase is a mixture of methanol—water—glacial acetic acid (66∶30∶4). UV detection was performed at 250 nm. The flow rate was 1.0 ml·min^-1.A good linearity was found at the concentration range from 0.5 to 100 μg·ml^-1, with the lowest detection limit 0.02 μg·ml^-1 (S/N=2). The extraction and method recoveries were 91.65% and 97.25% respectively,while the RSD for the withinday and betweenday precision were all less than 10%.The above method was applied to determine the plasma concentration of difunisal in three human volunteers after a single oral dosage of 300 mg. Two hours after administration, the plasma concentration of diflunisal reached maximum level. A two compartment method was used to study the pharmacokinetic parameters. The T_1/2α and T_1/2β were 1.40 h and 17.85 h, respectively.