Objective To improve a mouse model of autoimmune premature ovarian failure, different modeling times and adjuvant were used to determine factors related to induction of premature ovarian failure by zona pellucida glycoprotein 3 (ZP3). Methods B6AF1 mice with regular estrous cycles were randomly divided into five groups: normal, model A, model B, model C and model D groups. At the end of the experiment, serum was collected to detect sex hormones, and ovaries were collected to observe pathological changes, including effects on the zona pellucida and apoptosis of ovarian cells. Results Compared with the normal group, the model B, C and D groups showed estrous cycle disorders, including high gonadotropin and low estrogen levels, increased follicle atresia, obvious zona pellucida and increased apoptosis of ovarian apoptotic cells. The model C and model D groups had more obvious changes in the number of atretic follicles, ovarian apoptotic cells and zona pellucida. Conclusions In ZP3 induced autoimmune premature ovarian failure, the two-component model with three times immunization produced a stronger effect, and the modeling rate was 80%, which can be used as a reference for future modeling.