Abstract: Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. Glycyrrhiza glabra is an herb of Fabacea family which contain hypolipidemic compounds and flavonoids with high antioxidative properties. This study was conducted to determine the effect of Glycyrrhiza glabra extract on blood lipids and atherosclerosis in rabbits fed with high cholesterol diet. Fifteen male rabbits were randomly divided into three groups (normal diet group, high-cholesterol diet (1% cholesterol) and a group which received high-cholesterol diet supplemented with Glycyrrhiza glabra extract (50 mg/kg body weight every other day). The concentration of Total cholesterol (TC), LDL cholesterol, triglycerides (TG) and HDL cholesterol was determined in rabbits at the start of the experiment, and at the end of the first and second month of the study. At the end of the experimental period the aorta was removed for assessment of atherosclerotic plaques. Results show that Glycyrrhiza glabra significantly decreases TC, LDL and TG levels and increase HDL and lessens atherosclerotic lesion in aorta. Hence Glycyrrhiza glabra extract can effectively prevent the progress of atherosclerosis. This is likely due to the effect of Glycyrrhiza glabra on plasma lipoproteins and its antioxidant and anti-inflammatory properties