Aim To observe the influence of flu vast atin and simvastatin on atherogenesis and expression of vascular cell adhesion m olecule 1(VCAM 1) on aortic intima in ApoE deficient mice in order to investi gate the non lipid mechanisms of 3 hydroxy 3 methyl glutaryl coenzyme A(HMG CoA) reductase inhibitors on anti atherosclerosis. Methods Under the general feeding, pravastatin (every day 10 mg/kg) and sim vastatin (every day 5 mg/kg) were injected into the stomach of ApoE deficien t mice for 4 weeks . The areas of atherosclerotic plaques, and ratio of plaque area to aortic lumi nal area were detected by histochemistry technique. The expression of VCAM 1 o n aortic intima in ApoE deficient mice was detected by immunohistochemistry and Western blotting. Results Compared with controls, both of pravastatin and simvastatin could delay plaque formation in ApoE defic ient mice and diminish plaque size, and could inhibit VCAM 1 expression on aort ic intima, which were inconsistent with their cholesterol lowering effect. The inhibition of VCAM 1 expression by pravastatin or simvastatin in mice of 10 or 20 weeks old was slightly stronger than that in 30 weeks old mice. There was n o significant difference in inhibition of plaque information between pravastatin and simvastatin in view of the dosages used in this study. Concl usions The inhibitory effect of pravastatin and simvastatin on at h erogenesis of sclerotic lesions may crucially contribute to the clinical benefit s of HMG CoA reductase inhibitors on coronary artery disease. The inhibition o f VCAM 1 expression by pravastatin or simvastatin on aortic intima in ApoE def icient mice may play an important role in the reduction of VCAM 1 dependent mo nocytes adhesion to endothelium and reflect a new mechanism of statins on anti atherosclerosis, which is probably independent of lipid regulation.