Aim To observe the effect of Sini decoction on plaque area (PA), nitric oxide (NO), endothelin (ET), superoxide dismutase (SOD), malondiadehyde (MDA) in experimental atherosclerosis rabbits and study the possible mechanism. Methods Detect PA of aortic endothelium with image analysis method. Lipid metabolism with enzyme dynamics method , one-step method , formula method and immunization photoextinction in dividually. Serum NO and plasma ET with enzyme method and radioimmunoassay method in dividually. Plasma SOD and MDA with microcontent fast detecting method and modified Ba MuGuoFu method in dividually. Results Sini decoction can diminish lipid plaque area of aortic endothelium, reduce total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC), apolipoprotein B (apo B) and plasma ET, MDA, improve serum NO, apolipoprotein A (apo A) and plasma SOD content . Sini-high-dose group has the best effect in this experiment ,presenting with dose-effect dependent relationship. Conclusions Sini decoction has good effect against atherosclerosis, the possible mechanism maybe related to regulation of lipid metabolism and clearance of free radical oxygen and protection of vascular endothelium.