Aim To develop a rabbit model of vulnerable atherosclerotic plaque by cryogenic gas-induced endothelial injury combined with high-fat diet. Methods 24 healthy male New Zealand rabbits （3 months） were randomly divided into three groups: control blank group （group A）, sham-operated group （group B） and temperature control gas injury group （group C） with 8 in each group. After one week high-fat diet, the rabbits in group C were underwent carotid artery intima injury using cryogenic gas. The rabbits in group B suffered surgical operations without cryogenic gas. After the operation, the rabbits in group B and group C were kept feeding on high-fat diet for 12 weeks, whereas the ones in group A were kept on normal diet. All rabbits were killed after 13 weeks. Then paraffin-embedded and frozen sections were used for HE staining, Masson trichrome staining and elastic fiber staining and oil red O staining to analyze the changes of vascular morphology. Additionally, rat anti-rabbit macrophage antibody 11 （RAM11） monoclonal antibody was applied for animal immunohistochemistry staining. Results The rabbit carotid atherosclerosis established in our study was in line with the progress characteristics of vulnerable plaque, involving thin fibrous cap, large lipid core and macrophages and foam cells in the intima as well as endothelial cells shedding or local small scattered thrombosis. The rabbit carotid in sham-operated group showed intimal hyperplasia and partly showed small primary plaques infiltrated by macrophages, which was in line with the change of fatty streaks phase. There is no plaque visible in the control blank group. Conclusion It is viable and easy to develop a rabbit model of typical vulnerable atherosclerotic plaque by injuring carotid intima with temperature control gas combined with high-fat diet.