Aim To observe the effects of Sini decoction on atherosclerosis and oxidative injury in rabbits fed with cholesterol rich diet. Methods 24 rabbits were randomly divided into three groups. Normal group was fed with normal diet; Model group was fed 1% cholesterol and 5% fat diet; Sini decoction group was fed 1% cholesterol and 5% fat diet plus Sini decoction [2.1 g/(kg·d)]. At the end of study, the plaque area were measured, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of blood and aorta were detected. SOD protein and gene expression were observed with immunohistochemistry and hybridization in situ method. Results Compared with model group, Sini decoction could diminish lipid plaque area, intimal plaque area and intimal thickness, reduce the levels of aorta and serum MDA, increase aorta and serum SOD activity, increase the expressions of SOD protein and SOD gene in aorta. Conclusions The experimental results suggested that Sini decoction had antiatherogenic effects. The possible mechanism might be that Sini decoction could reduce oxidative injury in rabbits.