Lower limb amputation is a significant change in body structure. Loss of muscle, blood vessels, and blood leads to a redistribution of blood flow and changes in resistance at the end of blood vessels. In view of the significant increase in the prevalence of cardiovascular disease after lower limb amputation, the mechanism of which is still unclear, this study aims to establish an animal research model that can verify and explore the effects of amputation on cardiovascular system, and provide the experimental basis for subsequent animal experiments when exploring the effect of different amputation levels on the cardiovascular system. SPF New Zealand rabbits were divided into normal group ( n = 6) and amputation group ( n = 6). The amputation group was treated with above-knee amputation. The changes of low-density liptein cholesterol (LDL-C) and total cholesterol (TC) in serum of all the rabbits were monitored regularly after the surgery. The arterial pathological examination was conducted after the experimental rabbits were executed. The results showed that compared with the normal group, serum LDL-C content and TC content in the amputation group were significantly increased ( P<0.05); The blood vessels of the amputated rabbits had pathological changes such as degeneration and necrosis of smooth muscle cells in the middle membrane layer and rupture of elastic fibers. At the abdominal aorta and aortic arch, the elastic fiber area expression percentage (EFEP) of the experimental group was significantly lower than that of the normal group. The results suggest that the cardiovascular system of rabbits has the tendency of decreased arterial elasticity and lipid deposition in blood after amputation, indicating that the animal research model on the effect of amputation on the cardiovascular system has been successfully established, and can provide an experimental platform for further study on the mechanism of the effect of amputation on the cardiovascular system.