Abstract: AIM To establish an unstable atherosclerotic plaque model of common carotid artery in rabbits. METHODS Sixty New Zealand white rabbits were equally randomized into 3 groups: rabbits in group 1 (n=20) underwent balloon-induced arterial wall injury and then were given a diet of 1% cholesterol; rabbits in group 2 (n=20) were fed a diet of 1% cholesterol; and rabbits in group 3 (n=20) were fed a regular diet. After a 12 week diet, triggering of plaque disruption and thrombosis was attempted by injection of Chinese Russell’s viper venom (CRVV) and histamine. RESULTS In group 1, the stenosis in 38 lesions out of the 17 surviving rabbits were greater than 50％ with large lipid core and fibrous cap thinner than 65μm, and they were taken as unstable atherosclerotic plaques. In group 2, unstable atherosclerotic plaques were seen in 8 lesions of the 19 rabbits. In group 3, no unstable atherosclerotic plaques were seen. CONCLUSION An experimental animal model of unstable atherosclerotic plaque can be established by combining high lipid diet and balloon injury.