Hypolipidemic effect of Insamsansa-eum (ISE, Ren-Shen-Shan-Zah-Yin in Chinese) consisted of Red ginseng (RG; the steamed root of Panax ginseng C.A. Meyer) and Crataegii fructus (CF, the fruit of Crataegus pinnatifida BGE) is used frequently in China and Korea as a herbal medicine to treat arteriosclerosis, was investigated. Treatment of ISE significantly reduced blood triglyceride (TG) and total cholesterol (TC) levels in Triton WR-1339-induced hyperlipidemic mice and serum TG levels in corn oil-induced hypertriglyceridemic mice. ISE significantly lowered the high blood TG and TC levels as well as body and epididymal mass weights in hyperlipidemic mice induced by long-term feeding of a high-fat diet and increased blood HDL cholesterol level. ISE and its ingredients, RG and CF, inhibited pancreatic lipase and HMG-CoA reductase activities. Of its ingredients, RG reduced the blood TC level and HMG-CoA reductase activity more than CF. CF reduced blood TG level and pancreatic lipase activity more than RG. These finding suggest that the antihyperlipidemic effect of ISE may be due to synergistic inhibition of HMG-CoA reductase and pancreatic lipase by RG and CF, and that ISE may be effective hypolipidemic agents.