This study was to investigate the effects of Tongxinluo on adventitial vasa vasorum (VV) angiogenesis in early carotid atherosclerosis (AS). A rabbit model of AS was established by high-fat diet combined with encapsulation of left carotid artery. The rabbit models of AS were treated with high (0.6 g/kg/d)-, mid (0.3 g/kg/d)-, and low (0.15 g/kg/d)-dose Tongxinluo, respectively. Serum lipid levels were determined. Serum MDA level, SOD activity, and T-AOC level were assessed. Histological characteristics were detected with H&E staining. mRNA and protein expression levels were evaluated with quantitative real-time PCR and Western blot analysis, respectively. For the rabbit models of AS, Tongxinluo significantly alleviated the pathological changes, down-regulated mRNA and protein expression levels of VEGF and VEGF-R2, and reduced carotid VV angiogenesis. Moreover, compared with the model group, the Tongxinluo treatment reduced serum levels of TC and LDL-C, significantly down-regulated mRNA expression levels of TNF-alpha and IL-6, and significantly decreased protein expression levels of nuclear NF-kappa B, TNF-alpha, and IL-6. On the other hand, compared with the model group, the mRNA expression levels of NQO1 were up-regulated, and the protein expression levels of nuclear Nrf2 and NQO1 were increased, in the Tongxinluo treatment groups. Tongxinluo could reduce carotid adventitial VV angiogenesis and alleviate early AS lesions, through inhibiting carotid inflammation and oxidative stress injury.