Abstract: OBJECTIVE To observe the protective effect of Sanghuang decoction on oxidative damage induced by D-galactose in mice and explore the possible mechanism. METHODS ①The mice were divided into the normal group, the Sanghuang decoction low, middle, high dose(2, 6, 12 g·kg^-1) group, and administrated for 15 days. ②Mice were divided into the normal group, model group, vitamin E (50 mg·kg^-1) group, Sanghuang decoction low, middle, high dose(2, 6, 12 g·kg^-1) group. Subacute aging model was induced by subcutaneous injection of D-galactose(120 mg·kg^-1) into the neck and back of mice. The mice were continuous administrated for 42 d. The content of malondialdehyde(MDA) and activity of antioxidant enzymes such as superoxide dismutase(SOD), total antioxidant capacity(T-AOC) and peroxidase(POD) were measured by colorimetry in the liver and serum of mice. The levels of nuclear factor E2-related factor 2(Nrf2) and heme oxygenase 1(HO-1) proteins in liver were detected by Western blot. RESULTS Sanghuang decoction had no significant effect on body weight and organ index of normal mice and D-galactose induced mice. Sanghuang decoction could significantly improve the activity of T-AOC and SOD in the liver of normal mice(P<0.01, P<0.05). Sanghuang decoction could significantly increase T-AOC and reduce MDA content in serum of mice with aging model(P<0.01, P<0.05), meanwhile middle dose enhanced the activities of SOD(P<0.05) and POD(P<0.01), and middle and high dose upregulated the levels of Nrf2 and HO-1 proteins in liver of mice with aging model(P<0.01, P<0.05). CONCLUSION Sanghuang decoction can enhance the antioxidant capacity of normal mice and improve the oxidative damage induced by D-galactose, which maybe increase the activity of antioxidant enzymes in vivo, reduce the generation of lipid peroxide and improve the antioxidant capacity via Nrf2/HO-1 pathway.