This work is to investigate the joint effect of extract from Shenlian (SL, the Chinese abbreviation for Radix Salviae miltiorrhizae and Andrographis paniculata) and swimming on atherosclerosis prevention and treatment. Atherosclerotic rat model was established by combining low shear stress by partial ligation of common carotid artery with afterwards feeding of a hyperlipotic diet. Sprague-Dawley rats after partial ligation of common carotid artery were allotted to a 3 × 3 factorial design with three levels of swimming (0, 1, and 2 hr per day) and three levels of SL extract (0, 2.56, and 5.12 g/kg once daily p.o.) for a total of 9 treatment groups. Then, the feeding of the hyperlipotic diet and the intervention of swimming and SL started at the same time, and lasted for 8 weeks. By the end, blood samples were collected to determine blood viscosity, hematocrit, blood lipids, MCP-1, NF-κB and NO levels. The common carotid arteries of the rats were harvested to investigate pathological changes. The animal model showed early sign of atherosclerosis according to the pathological findings. Joint effects of SL extract and swimming on preventing atherosclerosis appeared significantly: The combination of 1 hour swimming with 2.56 g/kg SL extract showed to be effective for lowering hematocrit, blood viscosity (at 10 s(-1) and 200 s(-1)) and low-density-lipoprotein (p < 0.001). Combined treatment of 2.56 g/kg SL extract with 2 hr swimming led to a synergistic decrease in serum level of MCP-1. As a single factor, SL extract (2.56 g/kg) alone could decrease serum levels of NF-κB significantly (p = 0.003). Swimming alone could decrease cholesterol, triacylglycerols level and increase high-density-lipoprotein. The study demonstrates the combined therapy of oral SL extract with swimming on inhibiting inflammatory factors, improving hemorheological parameters and lipoproteins in rat model of atherosclerosis. It highlights the promising effects of the drugs and shear stress of blood flow, the biomechenopharmacological means, for prevention of atherosclerosis.