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AIM: To investigate the effects and mechanism of Xin-Tong-Tai granule on oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in mice with atherosclerosis (AS). METHODS: A total of 72 SPF-grade healthy male ApoEmice aged 6-8 weeks were fed with high-fat diet for 12 weeks to replicate AS models, and 12 SPF-grade healthy male C57BL/6J wild mice were fed with ordinary diet as the control group. After the corresponding drugs were administered for 8 weeks, the body weight and general condition of mice in each group were observed. The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected by biochemical kits. The pathological structures of aorta were observed by HE and oil red O staining. The levels of serum ox-LDL and aortic ICAM-1 and VCAM-1 were detected by ELISA. The protein levels of NADPH oxidase 4 (NOX4), NOX subunit p22phox, inhibitor of kB kinase-a (IKK-a), IKK-p and nuclear factor-KB (NF-kB) in aorta were detected by Western blot. RESULTS: Compared with control group, the mice in model group showed increased body weight (P<0. 05), dull and local shedding hair, slow grasping response, increased serum TC, TG and LDL-C levels, decreased serum HDL-C level (P< 0.05), increased the levels of serum ox-LDL and aortic ICAM-1 and VCAM-1 (P<0. 05), and increased protein expressions of NOX4, p22phox, IKK-a, IKK-p and NF-kB in aorta (P<0. 05). Compared with model group, the body weight of mice in each treatment group decreased (P<0. 05), the hair loss and the response flexibility were also improved. The serum levels of TC, TG and LDL-C decreased and HDL-C increased (P<0. 05). The levels of serum ox-LDL and aortic ICAM-1 (except the low-dose Xin-Tong-Tai granule group) and VCAM-1 decreased (P<0. 05). The protein levels of NOX4, p22phox, IKK-a, IKK-p and NF-kB in aorta decreased (P<0. 05). HE and oil red O staining showed that typical AS plaques could be seen in blood vessels of the model group, and the red-stained areas were widely distributed. The above lesions were alleviated to different degrees in each treatment group compared with model group. CONCLUSION: Xin-Tong-Tai granule reduces the atherosclerotic plaque area of Apoh mice induced by high-fat diet, decreased serum TC, TG and LDL-C levels, increased HDL-C level, decreased the levels of serum ox-LDL and aorta ICAM-1 and VCAM- 1,and inhibited protein expression of NOX4, p22phox, IKK-a and IKK-p in the aorta, thereby attenuating AS. [ABSTRACT FROM AUTHOR]