Objective To evaluate the effect of adventitia injury on atherosclerosis(AS)development, norepinephrine content, and sympathetic nerve density in the carotid artery of rabbits, so as to analyze the effect of Tongxinluo(TXL) on AS and the possible mechanism. Methods Totally 96 male rabbits with left carotid adventitia removed were fed with high cholesterol diet and were divided into two groups randomly:one group was lavaged with TXL (TXL group) and the other with water (adventitia injury group). In each group the adventitia of left cervical artery was injured and the right one served as control. The bilateral carotid artery specimens and blood samples were collected 1 d, 3 d, 7 d, 2 w, 4 w, and 8 w after the operation．The norepinephrine contents in serum and carotid artery were determined by ELISA and the density of the sympathetic nerve was analyzed by immnohistochemical method. Results In the adventitia injury group adventitia injury aggravated AS in the left carotid artery compared with that in the right carotid artery; the area of atherosclerotic plaque was positively correlated with the nerve density(r=0.94，P<0.05)and local norepinephrine content in the artery (r=0.90，P<0.05). TXL significantly decreased the area of atherosclerotic plaque compared to the advetitia injury group (IMR\[48±2\]% vs \[70±3\]%,P<0.01); besides, it also decreased the level of norepinephrine in the artery(\[83.76±3.3\] ng/g vs \[74.25±2.1\] ng/g, P<0.05)and the density of the sympathetic nerve(P<0.05). Conclusion Adventitia injury can promote the development of AS in high-cholesterol fed animals, partially through promoting the disorder of local sympathetic function, and TXL can inhibit the adventitia injury-induced AS.