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Background: Yindan Xinnaotong capsule has been used for treating cardio-cerebrovascular diseases for several decades in China. Exercise training can protect against the development of atherosclerosis. The aim of the present study is to evaluate the joint effect of YXC and exercise on atherosclerosis in rats. Methods: A combined method involving low shear stress and a high-fat diet was used to establish the atherosclerosis model in rats. Partial ligation of the left common carotid artery was performed, and then the rats were divided into 9 treatment groups according to a 3 x 3 factorial design with two factors and three levels for each factor, swimming of 0, 0.5,1 h daily and YXC administration of 0,1, 2 g/kg p.o. daily. Next the interventions of swimming and YXC were executed for 8 weeks. After that, blood samples were collected to determine blood viscosity, plasma viscosity, haematocrit (HCT), fibrinogen (FIB), blood lipid profile (including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C)), nitric oxide (NO), 6-keto- prostaglandin (PG) F1α, endothelin (ET) and thromboxane (TX) B2. The common carotid arteries of the rats were harvested to examine pathological changes, wall thickness and circumference, and the expression of SM22α was assayed via immune-histochemistry. Results: The early pathological changes were observed. The joint effects of YXC and swimming showed significant changes in the examined parameters: (1) decreases in plasma viscosity, blood viscosity and FIB; (2) increases in NO and 6-keto-PGF1α; (3) decreases in ET and TXB2; and (4) decreases in LDL-C and TG. The combination of 2 g/kg YXC and 1 h of swimming led to synergistic decreases in LDL-C and TG. The interactive effect between YXC and swimming was obvious in decreasing wall thickness. Swimming alone was able to up-regulate the expression of SM22α. Conclusions: In conclusion, this study indicates that the combination of YXC and swimming may prevent atherosclerosis through a synergistic effect between YXC and swimming in improving blood circulation, hemorheological parameters, blood lipids levels and the vascular endothelium in rats. The vascular remodeling may be contributed to the prevention effects on AS by up-regulating SM22α. [ABSTRACT FROM AUTHOR]