Aim To investigate the potential effects and molecular mechanisms of an angiotensin Ⅱtype 1 receptor blockers irbesartan on the process of atherosclerosis in high cholesterol-diet apolipoprotein E knockout(ApoE KO) mice. Methods Adult male ApoE KO mice were given normal diet or high cholesterol-diet and randomized to no treatment or irbesartan 10 mg/(kg·d) for 12 weeks.Systolic blood pressure was measured by a kind of non-invasive tail cuff system in conscious mice.The plasma total cholesterol and triglyceride concentration were measured by autoanalyzer.Atherosclerotic lesion area in aortic root was evaluated by oil red O staining.Inflammatory cytokines were measured by real-time reverse-transcription polymerase chain reaction(PCR) and Western blotting. Results The ApoE KO mice with high cholesterol-diet was associated with a marked increase in plasma lipid levels,atherosclerotic lesion area,as well as the expressions of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),monocyte chemoattactant protein-1(MCP-1) and vascular cell adhesion molecule-1(VCAM-1).These changes were suppressed in mice that were treated with irbesartan 10 mg/(kg·d) for 12 weeks concomitant with high cholesterol-diet administration,with no significant change in systolic blood pressure and plasma lipid levels. Conclusion The results suggest that irbesartan can attenuate atherosclerosis,and this effect is partly related to the inhibition of inflammatory response which leads to the decrease in the expression of inflammatory cytokines.