Objective Urotensin Ⅱ (U Ⅱ) is a vasoactive peptide of 11 amino acids, and may contribute to the development of atherosclerosis.The purpose of this study was to investigate whether U Ⅱ can promote the development of atherosclerosis in rabbits with high-cholesterol diet.Methods and Results U Ⅱ (low dose 2.7 μg/(kg · h);high dose 5.4 μg/(kg · h)) or vehicle was infused into White Japanese rabbits with high-cholesterol diet for 16 weeks through an osmotic mini-pump.Aortic atherosclerotic lesion and the cellular component of macrophage and smooth muscle cell in aortic arch atherosclerotic lesions were examined.With low dose of U Ⅱ infusion, aortic atherosclerosis and cellular components (macrophage and smooth muscle cell) in atherosclerotic lesion were unchanged between U Ⅱ group and vehicle group.Chronic U Ⅱ infusion with high dose significantly resulted in increased aortic atherosclerotic lesions by 21% (P <0.01) in total aorta, 24% (P <0.01) in aortic arch, 11% (P =0.054) in thoracic aorta,18% (P <0.05) in abdominal aorta, without affecting the plasma levels of total cholesterol, high-density lipoprotein cholesterol, triglyceride and body weight.Immunohistochemical staining showed that macrophages were significantly increased in the atherosclerotic lesion of aortic arch in the high dose U Ⅱ infusion group.However, there was no significant difference in smooth muscle cell of aortic atherosclerotic lesions between the two groups.Conclusions In conclusion, our results proved U Ⅱ promote the development of atherosclerotic lesion in rabbits, and enhanced the cellular component of macrophage in the aortic arch atherosclerotic lesion.