Background and Aims: Losartan, angiotensin II receptor blockade, is mainly used as antihypertensive medicine, but not much for its antiatherosclerotic purpose. Simvastatin is a HMG-CoA reductase inhibitor and has been shown to reduce LDL concentrations and decrease the coronary events and stroke in the patients with coronary heart disease. We tried to see whether losartan and/or simvastatin have any anti-atherosclerotic effects on apoE (-/-) mice. Methods: Apo E (-/-) mice were fed high-fat high-cholesterol (HFHC) diet (0.3% cholesterol) for 10 weeks with and without cotreatment of losartan (40mg/kg) and simvastatin (40mg/kg). Apo E (-/-)mice were divided into four groups. Control (normal chow fed, n=5), HFHC diet (n=5), HFHC diet with losartan (n=5), HFHC diet with simvastatin (n=5), and HFHC diet with both losartan and simvastatin. Results: Losartan cotreatment in apoE(-/-) mice showed significantly decreased atherlsclerotic lesion area in whole aortic strip stained with oil red O. Plaque area measured at the aortic sinus level was also significantly reduced in the losatan cotreated group. In the HFHC only given mice smooth muscle cell layer was almost disappeared in the aortic media. Smooth muscle cell layer in aortic media was over 60% preserved in the losartan cotreated group. Simvastatin cotreatment with HFHC diet also decreased atherosclerotic lesion area and decreased plaque area. Simvastatin also preserved smooth muscle cell layer in aortic media by over 50%. Losartan���s antiatherosclerotic effects looked a little stronger than simvastatin. Cotreatment with both losartan and simvastatin showed greater antiatherosclerotic effects compared with each drug only treated group. Serum lipid profiles were not significantly different between each group. Conclusions: These results suggest that losartan has anti-atherosclerotic effects in the apoE(-/-) mice which is equivalent or greater than simvastatin and both drugs together looks to show greater antiatherosclerotic effects.