Objective To explore an establishment method and influencing factors of an intimal hyperplasia model of common carotid artery in rabbits. Methods Thirty New Zealand white rabbits, half male and half female, were randomly divided into a sham operation group, high fat + unilateral cannula group (divided into 2- and 3-week subgroups in accordance with the modeling time), and hyperlipidemia + bilateral cannula group ( divided into 2 - and 3-week subgroups in accordance with the modeling time). In the unilateral cannula group, a silicone tube (20 mm in length and inner diameter of 1 mm) was placed on the lateral side of the left common carotid artery and fixed, whereas in the bilateral cannula group, a silicone tube was placed on the lateral side of the bilateral common carotid artery and fixed. Both groups were fed a 2% cholesterol diet for 2-3 weeks starting from the day after the operation. In the sham operation group, the common carotid artery was separated, no vascular cannula was performed, and the rabbits were fed a regular diet. At 2 and 3 weeks after the operation, pathomorphological changes of the injured common carotid artery were observed, the index of intimal hyperplasia was measured by morphometry, and expression of α-smooth muscle actin ( α-SMA), osteopontin (OPN), type I collagen (Col-Ⅰ), inflammatory response factor interleukiN-1β ( IL-1β), and tumor necrosis factor-α (TNF-α) in intimal hyperplasia was determined by immunohistochemistry. Results After treatment with high fat and the silicone tube for 2 or 3 weeks, intimal hyperplasia was found in the common carotid artery. The intimal area, intimal thickness, intimal area proliferation rate, and intimal thickness were increased significantly. Intimal hyperplasia in the bilateral cannula was more obvious than that in the unilateral side, and intimal hyperplasia at 3 weeks was more serious than that at 2 weeks. After 3 weeks of the bilateral cannula, expression of α-SMA in the vascular intima was reduced significantly and expression of OPN, Col-Ⅰ, IL-1β, and TNF-α was increased significantly. Conclusions A model of intimal hyperplasia can be successfully established using high fat and a common carotid artery silicone cannula, and the bilateral common carotid artery cannula should be applied for more than 3 weeks.