Aim To establish a novel animal model to study the mechanism of autologous vein graft atherosclerosis and methods of preventing vein graft atherosclerosis. Methods 30 male New Zealand White rabbits were randomly assigned to normal control group (rabbits fed by normal diet, n=6), vein graft group (rabbits treated by autologous external jugular vein grafting to common carotid artery and fed by normal diet, n=12) or vein graft plus high-fat diet group (rabbits treated by autologous vein graft and fed by high-fat diet, n=12). Animals were sacrificed at 12 weeks after surgery. Serum lipid levels were measured and vein grafts were investigated by light microscopy and transmission electron microscopy. Results Hyperlipidemia and the typical atherosclerotic lesions of vein grafts were observed in the vein graft plus high-fat diet group. The lesion included intimal hyperplasia, the migration and proliferation of smooth muscle cells, the accumulation of lipid and cholesterol and the formation of foam cells. But only intimal hyperplasia and the migration of smooth muscle cells were observed in the vein graft group. There were no obvious changes in the external jugular veins of the normal control group. Conclusions The autologous typical vein graft atherosclerosis can be induced by autologous external jugular vein graft plus high-fat diet in rabbits. The animal model was suitable for the advanced research in the mechanism and prevention of human autologous vein graft atherosclerosis.