The aim of the present paper was to investigate the effect of Shengjie Tongyu granule on vascular remodeling in atherosclerotic mice and the relevant underlying mechanism. Sixty male ApoE-gene-knockout mice, fed a high-fat diet from 6 weeks of age, were randomized into a Shengjie Tongyu granule group (4.00 g/kg/d), a simvastatin group (9.01 mg/kg/d), and a control group (normal saline: 0.2 mL/d). At the ages of 30 and 40 weeks, we sacrificed the mice for various measurements. The results show that treatment with Shengjie Tongyu granule and simvastatin significantly decreased lumen and plaque areas in the aortic root at 30 and 40 weeks of age, decreased grade II elastic fiber lesions in the ascending aorta at 30 weeks of age, and decreased both grade II and III lesions at 40 weeks of age, compared to controls. The content of superoxide anions, and expression of MOMA-2, plasma ICAM-1, and NF kappa B p50 in 30- and 40-week-old mice in the Shengjie Tongyu granule and simvastatin groups were also significantly reduced compared to the control group. In conclusion, Shengjie Tongyu granule has a clear inhibitory effect on vascular remodeling and on inflammatory pathways in ApoE-gene-knockout mice.