The purpose of this study was to investigate the protective effect of salvianic acid A (SAA) against atherosclerosis in rats and the mechanisms. The rats were randomly divided into control, model, atorvastatin and SAA groups. The atherosclerosis model was established in model, atorvastatin and SAA groups by intraperitoneal administration of 150 kU/kg vitamin D3 and fed with high-fat diet during 8 weeks. Then, the atorvastatin group was treated with 4.8 mg/kg atorvastatin by gavage for 8 weeks, and the SAA group was treated with 80 mg/kg SAA by gavage for 8 weeks. After treatment, compared with model group, in SAA group the total cholesterol, triglyceride and low-density lipoprotein cholesterol levels significantly decreased, the serum high-density lipoprotein cholesterol level significantly increased, the whole blood viscosity, plasma viscosity, hematocrit and platelet adhesion rate significantly decreased, the serum catalase, superoxide dismutase and glutathione peroxidase levels significantly increased, the serum malondialdehyde level significantly decreased, the serum tumor necrosis factor a, interleukin 6, interleukin 1 beta and C-reactive protein levels significantly decreased, and the abdominal aorta Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor kappa-B p65 protein expression levels significantly decreased. In conclusion, SAA can alleviate the atherosclerosis in rats by enhancing the blood lipid profile, improving the hemorheology, reducing the oxidative stress, decreasing the inflammatory response and down-regulating the TLR4/MyD88/NF-?B signal pathway.