OBJECTIVE Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti-tumorigenic properties that is beneficial in defending against NASH and was recently proved to be an Nrf2 activator. The aim of this study was to evaluate whether Nrf2 activation could be involved in NASH mitigation by curcumin. METHODS Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2 protein expression were explored in adult Sprague-Dawley rats developing high-fat-diet-induced NASH and submitted to curcumin gavage for 6 weeks. RESULTS Curcumin administration led to lower degrees of hepatic steatosis and inflammation; lower levels of serum aminotransferases, lipids, and homeostasis model assessment of insulin resistance; and lower serum and hepatic contents of tumor necrosis factor-α (TNF-α), interleukin-6, and malondialdehyde. In contrast, higher hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei was significantly higher in rats with curcumin. CONCLUSIONS Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.