BACKGROUND Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis associated conditions, such as Coronary Heart Disease (CHD), ischaemic cerebrovascular disease and peripheral vascular disease. Though there are hypolipidemic drugs available, the search for a more efficacious hypo lipidemic agent was always going on. OBJECTIVE To study the effect of Silybin on lipid profile in Hypercholesterolaemic rats. METHODS After grant of permission from animal ethics committee, the animals were divided into four groups of eight each (normal control, Experimental control with High cholesterol diet, High cholesterol diet + Silybin 300mg, High cholesterol diet + Silybin 600mg). At the end of 60 days the animals in all the groups were subjected to overnight fasting followed by plasma and liver biochemical analyses. METHODS The data were analysed by ANNOVA followed by Duncan's multi range test and the value of p≤0.05 was used as the criterion for statistical significance. RESULTS The rats fed on high cholesterol diet showed significant increase in serum total cholesterol, Triglycerides, LDL-C and VLDL-C. Treatment with Silybin significantly decreased serum total cholesterol (24%), Triglycerides (21%), LDL-C (24%) in a dose dependent manner. Rats treated with Silybin (300 and 600 mg/kg) showed significant increase in hepatic HDL -C and decrease in other lipid profiles. CONCLUSIONS Treatment with Silybin significantly decreased both serum and hepatic total cholesterol, triglycerides, VLDL-C, LDL-C and increased HDL-C at both doses.