Objective: To investigate the effects of pterostilbene on oxidative stress and apoptosis in nonalcoholic fatty liver disease(NAFLD) rats by regulating Kelch-like ECH-associated protein 1(Keap-1)/nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway. Methods: 60 SD rats were randomly divided into control group, model group, pterostilbene low-dose group(30 mg/kg), pterostilbene high-dose group(60 mg/kg), pterostilbene(60 mg/kg)+N-(4-(2,3-dihydro-1-(2’-methylbenzoyl)-1H-indole-5-yl)-5-methyl-2-thiazolyl)-1,3-benzodioxazol-5-acetamide(ML385)(30 mg/kg) group, with 12 rats in each group. Rats in model group and drug intervention group were fed with high-fat diet to induce NAFLD model, and rats in control group were fed with normal diet, each group was continuously fed for 12 weeks. 14 days after treatment with pterostilbene and ML385 groups(control group was treated with the same dose of normal saline), the lipid metabolism indexes [triglyceride(TG), total cholesterol(TC) and free fatty acid(FFA) levels], liver index, liver function indexes [alanine aminotransferase(ALT) and aspartate aminotransferase(AST)] levels,serum interleukin(IL)-17, IL-6, IL-10, oxidative stress indexes [malondialdehyde(MDA), superoxide dismutase(SOD) and catalase(CAT)] levels were detected in each group. The apoptosis rate of hepatocytes in each group were detected by in situ end labeling method(TUNEL) staining. The expression of apoptosis-related proteins and Keap-1/Nrf2/HO-1 pathway-related proteins in liver tissue of rats in each group were detected by western blotting. Results: Compared with control group, the levels of serum IL-10, SOD and CAT, the expression levels of Nrf2, HO-1 and Bcl-2 in liver tissue of rats in model group were significantly decreased(P<0.05), and the levels of TG, TC and FFA, liver index, ALT and AST levels, serum IL-17, IL-6, MDA levels, hepatocyte apoptosis rate, liver tissue Keap-1 and Bax expression levels were significantly increased(P<0.05). Compared with model group, the levels of serum IL-10, SOD and CAT, the expression levels of Nrf2, HO-1 and Bcl-2 in liver tissue of rats in pterostilbene low and high dose groups were increased(P<0.05), and the levels of TG, TC and FFA, liver index, ALT and AST, serum IL-17, IL-6, MDA, hepatocyte apoptosis rate, the expression levels of Keap-1 and Bax in liver tissue were decreased(P<0.05). Compared with pterostilbene low-dose group, the levels of serum IL-10, SOD and CAT, and the expression levels of Nrf2, HO-1 and Bcl-2 in liver tissue were increased in pterostilbene high-dose group(P<0.05), and the levels of TG, TC and FFA, liver index, ALT and AST, serum IL-17, IL-6, MDA, hepatocyte apoptosis rate, and the expression levels of Keap-1 and Bax in liver tissue were decreased(P<0.05). Compared with pterostilbene high-dose group, the levels of serum IL-10,SOD and CAT, and the expression levels of Nrf2, HO-1 and Bcl-2 in liver tissue of pterostilbene+ML385 group were decreased(P<0.05),and the levels of TG, TC and FFA, liver index, ALT and AST, serum IL-17, IL-6, MDA, hepatocyte apoptosis rate, and liver tissue Bax expression level were increased(P<0.05). Conclusion: Pterostilbene may improve lipid metabolism, regulate inflammatory response and oxidative stress, and reduce hepatic steatosis and apoptosis in NAFLD rats by activating Keap-1/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]