This study was to explore the possible effects of luteolin on ApoE-/-mice with non-alcoholic steatohepatitis induced by high fat diet as well as the efficacy on atherosclerosis. Methods: The model was induced by high fat diet, and luteolin were administered by gastric perfusion at 70 and 140 mg/kg qd for 12 weeks. The serum level of superoxide dismutase(SOD), malondialdehyde(MDA), glutathion peroxidase(GSH-Px)were measured. The contents of alanine transaminase(ALT), aspartate aminotransferase(AST)were measured in liver tissue of grout. The pathological changes of liver tissue were examined by HE staining and the lipid accumulation in the liver and aortic root was tested by oil red O staining. The apoptotic hepatocytes were detected by TUNEL assay and the expression levels of Bcl-2 and caspase-3 were observed by immunohistochemisty. Results: The results showed that Luteolin(70, 140 mg/kg)improved the liver function significantly through reducing the level of ALT, AST, and increasing the content of SOD, GSH-Px and Bcl-2 while reducing the content of MDA, lipid accumulation, hepatic steatosis, TUNEL-positive cells and the expression of caspase-3. Conclusion: The results suggest that Luteolin may inhibit the liver injury and atherosclerosis induced by high fat diet by decreasing the oxidative stress.