Aim The present study was undertaken to investigate the possible mechanism of Tongxinluo on preventing vasoconstriction and vascular hypersensitivity to 5-hydroxytryptamine induced by the injury of the adventitia. Methods Wistar Kyoto rats were assigned to 4 treatments(n=12 for each group): vehicle,low dose of Tongxinluo [200 mg/(kg·d)],middle dose of Tongxinluo [400 mg/(kg·d)] and high dose of Tongxinluo [800 mg/(kg·d)].After 1 week of treatment,adventitia injury was induced by positioning a silicone collar around the right carotid artery for one week.Blood flow and vascular reactivity to serotonin were determined 1 week after injury,the blood from the rat's heart was taken to measure the concentration of angiotensinⅡ(Ang Ⅱ) in the serum with the ELISA,and both side of carotids were harvested for RT-PCR analysis. Results Collar-induced adventitia injury decreased the carotid blood flow(P>=0.0002),increased the vascular reactivity sensitivity to 5-hydroxytryptamine,and upregulated the expression of AngⅡ type 1(AT1)receptor(135% increase,P>=0.0020),Ang ⅡII type 2(AT2)receptor(76% increase,P>=0.0061),and p22phox(2.89 fold increase,P><0.0001)in collared arteries.Low dose of Tongxinluo did not affect vasoconstriction function,serum AngⅡconcentration,or the expressions of AngⅡ receptors and p22phox.Treatment with medium dosage and high dosage of Tongxinluo can effectively improve the carotid blood flow,normalize the hypersensitivity to 5-hydroxytryptamine(all with P><0.05),lower serum AngⅡ concentration(middle dosage group:26.31±6.82 ng/L vs 45.21±4.52 ng/L,P>=0.0480;high dosage group: 20.51±2.51 ng/L vs 45.21±4.52 ng/L,P>=0.0183),restrained the increase of p22phox expressions(79.1% decreasing in middle dosage group,P>=0.0002;83.2% decreasing in high dosage group,P>=0.0001),did not affect the AT1 receptor expression,while high dose of Tongxinluo increased AT2 receptor expression. Conclusion Tongxinluo can effectively prevent the vasoconstriction and the vascular hypersensitivity to 5-HT induced by the adventitia injury in rat carotid through lowering serum AngⅡ level and restraining the significantly enhanced oxidative stress induced by the adventitia injury.