Aim To investigate the effects of Losartan on expression of mitogen-activated protein kinases (MAPK) and vessel proliferation in a rabbit model of early accelerated atherosclerosis. Methods Aortic cholesterol content, expression of proliferation cell nuclear antigen (PCNA) and MAPK protein were detected by enzymatic analysis and immunohistochemistry. Results The ratio of vascular intimal to medial thickness, numbers of positive PCNA cells, and expression of MAPK protein in As group singnificantly increased compared with control group. There was a significant decrease in the ratio of vascular intimal to medial thickness, numbers of positive PCNA cells and expression of MAPK protein (p<0.001) in the Losartan-pretreated group. Aortic cholesterol content in the Losartan-pretreated group was significantly decreased compared with As group (p<0.05). Conclusion Losartan inhibits vascular MAPK expression, intimal proliferation and decreases cholesterol deposit in vascular walls which may play an important role in prevention of atherosclerosis.