Aim To observe the therapeutic effect of soybean isoflavones (SI) on the expression of peroxisome proliferator activated receptor α (PPARα), nuclear factor-kappa B(NF-κB), vascular cell adhesion molecule-1(VCAM-1), and investigate its mechanism of anti-atherosclerosis in metabolic syndrome rats. Methods Sixty male SD rats were randomly divided into normal diet group (n=10)and high-fat diet group (n=50)to induce metabolic syndrome model. Rats in high-fat diet group were fed with high-lipid high-salt high-sugar food for 20 weeks. After 20 weeks 37 metabolic syndrome rats were got successfully, and then these 37 metabolic syndrome rats were randomly divided into model group(n=9), fenofibrate-treated group(n=8), low dose (90 mg/kg) SI-treated group (n=10) and high dose (360 mg/kg) SI-treated group(n=10). Blood lipid level was measured after 4 weeks and mRNA level of PPARα of rat liver was determined using fluorescent quantitative PCR (FQ-PCR). The expressions of NF-κB and VCAM-1 of rat aorta were observed by immunohistochemistry. Results In high dose SI-treatment group, the low density lipoprotein cholesterol (LDLC),triglyceride (TG) and total cholesterol (TC) levels were significantly lower than those in model group(P<0.01), while the expression of PPARα was increased compared with model group. The expressions of NF-κB and VCAM-1 in model group were higher than those in control group. Compared with model group, high-dose SI decreased the expressions of NF-κB and VCAM-1 on the rat aorta. Conclusion SI can regulate the blood lipid level in metabolic syndrome rat, reduce the level of atherosclerosis factor, and can effectively stop the formation of atherosclerosis. Its mechanism may be associated with up-regulating the expression of PPARα mRNA by SI.