For routine analysis of diclofenac sodium in plasma, a new high performance liquid chromatographic method, which is combined with column-switching technique is developed. The precolumn packed with Corasil RP C-18 was connected to analytical column by switching system in order to enrich the sample drugs in plasma without extraction. This method showed excellent sensitivity, precision and reproducibility. The limit of detection, using a 100 microL injection of plasma, was 0.1 micrograms/mL and the mean coefficient of variation for intra- and inter-assay was better than 4.6%. Total analysis time was 20 min between injections. The present method offers distinct practical advantages over conventional liquid-liquid extraction methods of sample preparation with respect to time, effort, recovery, and sample volume required. The method has been applied to the samples from rats receiving oral administration of diclofenac sodium.