Aim To explore the relationship between adipophilin and atherosclerosis. Methods The New Zealand white rabbits were fed with high cholesterol chow for 12 weeks and became the model of atherosclerosis. The level of serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride, and cholesterol content of aortic wall were investigated. The areas of fatty streak of the aortae were measured after staining with Sodan Ⅳ. The aortic, and live specimens with HE and immunohistochemstry staining were observed with light microscopes. Results In the animals fed with high cholesterol chow, the level of serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride, and cholesterol content of aortic wall significantly increased. The areas of fatty streak in the aortae was 40.1%±7.3% at the end of 12 weeks. The fatty streak of the aorta with immunohistochemstry staining was strongly positive, and the liver was negative with or without high cholesterol chow. Conclusions The New Zealand white rabbits could be made the model of atherosclerosis through feeding with high cholesterol chow for 12 weeks. Expression of adipophilin in atherosclerotic rabbits increased,which suggested the adipophilin was related to the development of atherosclerosis.