Aim To evaluate the effect of angiotensin Ⅱ type 1 receptor antagonist Irbesartan on the expression of vascular cell adhesion molecule-1 (VCAM-1)in a rabbit model of high cholesterol diet induced atherosclerosis. Methods Twenty-five rabbits were divided into three groups: control group, high cholesterol group, Irbesartan group [50 mg/(kg·d)]. The later two groups received 1% cholesterol diet for 12 weeks to establish the early atherosclerosis model. Blood samples were collected for cholesterol assessment and angiotensin Ⅱ concentrations. The levels of expression of VCAM-1 mRNA were evaluated by RT-PCR and Northern Blot. Results There is no difference between the two high-cholesterol groups, although the cholesterol level of these groups are much higher than control group. Rabbits received Irbesartan showed reduced intimal thickness and the ratio of aortic intimal thickness to medial thickness compared with high cholesterol group (P<0.05). Irbesartan administration for 12 weeks caused a down-regulation in arterial expression of VCAM-1 normalized to GAPDH (P<0.05). Conclusion Chronic Irbesartan treatment ameliorated the severity of the early atherosclerosis lesions, possibly because of the suppression of VCAM-1 mRNA expression.