The preventive hypolipidemic effect of the aqueous extracts of Picrorrhiza Rhizoma (PR) was observed in a high fat diet (HFD) feeding hyperlipidemic mouse with their hepatoprotective effects. PR extracts (50, 100 and 200mg/kg) were orally dosed once a day for 12 weeks initiated with HFD supply, and changes on body weight and gains, liver weight, serum aspartate transferase (AST) and alanine transferase (ALT) levels were monitored with serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels. The efficacy of test articles was compared to that of 10mg/kg of simvastatin (SIMVA). Dramatic decrease of both absolute and relative liver weight was dose-dependently observed in all PR extract dosing groups as compared with HFD control group. The serum AST and ALT levels were dose-dependently decreased in PR extract dosing groups. The serum LDL, triglyceride and total cholesterol levels were dose-dependently decreased in PR extract dosing groups compared to that of HFD control group. The serum HDL levels were slightly but dose-dependently increased in PR extract dosing groups as compared with control group. The efficacy on the serum lipid levels of PR extracts was slighter than that of SIMVA. Based on these results, it is concluded that water extract of PR has a relatively good favorable preventive effects on the HFD inducing hyperlipidemia and hepatopathy.