Aim To establish a new animal model which is more suitable for the study on carotid atherosclerosis and to investigate its mechanisms. Methods 54 male Japanese White rabbits were randomly divided into 3 groups. The first group was fed by normal diet as blank control (n=6), the second group was fed by high cholesterol diet as cholesterol fed control groups (n=24), the third group was fed by high cholesterol diet and treated by air drying as experimental groups (n=24). Animals were sacrificed at various times (from 3 days to 4 weeks) after surgery in the experimental groups and at the corresponding times in the control groups. The carotid arteries were prepared for examination by light microsocopy and by transmission electron microsocopy. The intimal thickening were evaluated by intimal area/medial area ratio(I/M ratio). Results The typical carotid atherosclerosis was observed in the experimental groups. The changes included endothelial regeneration, the proliferation of smooth muscle cells and monocytes, significant intimal thickening and secondary vascularization in intimal, the formation of connective tissue matrix comprising elastic and collagen, the accumulation of lipid and cholesterol in the associated cells and in the surrounding matrix. The neointimal thickening was significant at 2 week and 4 week in the experimental groups and the I/M ratio reached 0.47±0.07 and 0.94±0.07. Conclusions The typical carotid atherosclerosis lesion can induced by cholesterol diet plus air drying in rabbit. The pathological changes and its mechanisms were more suitable for the advanced research in experimental carotid atherosclerosis.