Objective To observe the protective effect of resveratrol in mice with premature ovarian failure and to explore its possible mechanism. Methods Forty two-month-old female mice were randomly divided into four groups: control group (Control), model group, 20 mg / kg RES group, and 40 mg / kg RES group with 10 mice in each group. Changes in body weight and the ovarian weight coefficient were assessed. Follicle number changes in mouse ovarian tissue were observed by HE staining. Relative mRNA expression of cyclin D1, Wnt1 and β-catenin in ovarian tissues was measured by RT-qPCR. β-catenin protein expression in ovarian tissue was detected by immunohistochemical staining. Mvh, Oct4, SOD2, Nrf2, Bax and Bcl-2 protein expression in ovarian tissues was detected by Western blot. Results Body weight, ovary weight, and ovary / mouse weight ratio in 20 and 40 mg / kg RES groups were higher than those in the model group. Compared with the model group, the number of primordial follicles was increased and the number of atresia follicles was decreased in 20 and 40 mg / kg RES groups (P<0. 05), while mRNA expression of cyclin D1, Wnt1 and β- catenin was increased in ovarian tissues (P<0. 05). Compared with the model group, β-catenin protein expression was increased in ovarian tissues in 20 and 40 mg / kg RES groups in a concentration-dependent manner. Compared with the model group, Mvh, Oct4, SOD2, Nrf2 and Bcl-2 protein expression was increased and Bax expression was decreased in ovarian tissues of 20 and 40 mg / kg RES groups (P<0.01). Conclusions The protective effect of resveratrol in mice with premature ovarian failure may be related to inhibition of ovarian cell apoptosis and activation of the Wnt / β-catenin pathway to promote recovery of ovarian functions.