The objective of this study was to investigate the protective effect and the mechanism of allantoin (ALL) from Dioscoreae Rhizoma on ovaries of rats with premature ovarian failure.A one-time intraperitoneal injection of 75 mg/kg cyclophosphamide was used to create a model of premature ovarian failure in SD rats,and ALL was administered.Ovarian index,follicle development in pathological sections and serum hormone levels were used to assess the ovarian function of the rats.Superoxide dismutase (SOD),glutathione peroxidase(GSH-Px) and malondialdehyde (MDA) levels of ovary were detected by colorimetry.Immunohistochemistry and Western blotting were used to detect nuclear factor erythroid-2 related factor 2 (Nrf2),heme oxygenase-1(HO-1) and NAD(P)H quinone dehydrogenase 1(NQO1) protein expressions.The results show,compared with the nomal contol (NC) group,the ovarian index and the level of estradiol (E2) in POF group were decreased (P<0.05 or P<0.01),the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were increased (P<0.05 or P<0.01),the primary,secondary and mature follicles in ovarian tissue were decreased,and the atretic follicles were increased.SOD and GSH-Px,Nrf2 and HO-1 levels in tissue homogenate were significantly decreased (P<0.05 orP <0.01),while the MDA level was significantly increased (P<0.05).After 14 days of treatment,compared with POF group,ALL increased the level of E2,decreased the levels of LH and FSH in the POF rats(P<0.05 or P<0.01),and increased primary,secondary and mature follicles in ovarian tissue of POF rats.The levels of SOD,GSH-Px,Nrf2,NQO1 and HO-1 were increased (P<0.05 or P<0.01),and the levels of MDA were decreased (P<0.05).Allantoin from Dioscoreae Rhizoma modifies oxidative stress in rats with premature ovarian failure through Nrf2/HO-1 pathway,and has protective effect on the ovaries of rats.