The pharmacokinetics of paeoniflorin (PAE) was examined after an iv dose of 20, 40, or 100mg/kg in rats. The decline of plasma concentration was biexponential after each dose. Dose, however, had a marked effect on the pharmacokinetics, with a greater than proportional increase in AUC at 100mg/ kg, even though the increase was proportional at the dose range from 20 to 40mg/kg. There was also significant decrease of the steady-state distribution volume (Vdss), and total body (CLtot), and renal (CLR) clearances at the high dose (p<0.01 or 0.05), without a significant difference between the two low doses. Plasma unbound fraction (0.75) was constant over the observed range of plasma PAE concentrations (0.8 ?? 700μg/ml). The decrease of Vdss was ascribed to the dose-dependent Kp values in liver, kidney, gastrointestinal tract, and skin. The significant decrease of biliary clearance (CLB) at 100mg/kg as compared with that at 20 and 40mg/kg contributed to the decrease of CLtot. It was suggested that the decreases of CLB and CLR may be a consequence of saturable transport from plasma into liver, and the significant decrease of glomerular filtration rate (p<0.05) at the higher steady-state plasma level than at the lower plasma levels might be owing to a decreasing effect of PAE on renal plasma flow, because transport from liver to bile did not appear to be saturable, and the excretion into urine seemed to occur only by glomerular filtration. Thus, the pharmacokinetics of PAE in rats was dosedependent.