OBJECTIVE To establish a HPLC method for the determination of protocatechuic acid(PA)in rat plasma and tissue.METHODS A single oral dose of PA was performed in rats at 12.5,25,50 mg·kg-1,plasma concentrations at eachtime point were determined by HPLC and the data were analyzed by DAS 2.0.The concentrations of PA in the main tissues were determined at 10,30 and 60min after an oral administration of 25 mg·kg-1.RESULTS The pharmacokinetics of PA conformed to a two-compartment open model after ig administration.The main pharmacokinetic parameters were Cmax(mg·L-1):0.34±0.06,1.59±0.07,3.03±0.34;AUC(0-t)(mg·min·L-1):38.97±4.35,147.53±17.35,423.64±61.58.PA was mainly distributed in stomach,kidney,heart,less in liver,muscle and spleen,and least in brain and lung.CONCLUSION A simple,rapid,accurate and precise HPLC method for the analysis of PA in rat plasma was successfully developed and validated and successfully applied to a pharmacokinetic and tissue study of PA in rats.