Abstract: The concentrations of berberine(BBR)and 8-cetylberberine(8-BBR-C16)in rat plasma and tissue were determined by RP-HPLC. Both the plasma pharmacokinetics characteristic and tissue distribution differences of BBR and 8-BBR-C16 were compared to provide experimental data for the mechanism research and further drug development. After the oral administrations of BBR and 8-BBR-C16 at the dose of 80 mg·kg^-1 for rats, the pharmacokinetics result showed that compared with BBR, the C_max and AUC_0-t of 8-BBR-C16 increased by 2.8 times and 12.9 times respectively, t_l/2 extended from 3.61 h to 11.90 h. The tissue distribution result showed that compared with BBR, the concentration of 8-BBR-C16 in various organizations increased and the retention time extended remarkably. The maximum concentration was achieved in lung and the highest concentration in it was 3 731.82 ng·g^-1. After being derived, the C_max in plasma and bioavailability of 8-BBR-C16 increased remarkably and the circulation time in vivo extended. The drug concentration in tissue increased remarkably, and the distribution ratio changed too, with strong targeting selection in lung.