Objective Changes in relevant indexes in the mouse model of early-onset ovarian insufficiency caused by Tripterygium wilfordii polyglycoside were analyzed, and the optimal time point for intervention was determined. Methods Forty female ICR mice were randomly divided into control and A, B, C, and D model groups with eight mice in each group. The control group was gavaged with purified water for 14 days ( 0. 01 mL / 10 g) , and the remaining groups were administered a Tripterygium wilfordii polyglycoside suspension (80 mg / kg, 0. 01 mL / 10 g) for 1 day (A model group) , 3 days (B model group) , 7 days (C model group) , or 14 days (D model group) , and samples were collected. Body weight and wet weights of the uterus and bilateral ovaries of mice were determined in each group. Serum FSH, LH, E2, P,AMH, INH-B, and T contents were measured using enzyme-linked immunoassays. HE staining was used to observe the number and developmental status of follicles and corpus luteum at all levels in mice of each group. TUNEL staining was used to detect the apoptosis in the ovaries of mice in each group. IHC detected expression of VEGFA, CD34, and EPO proteins in the ovaries of mice in each group. mRNA expression of HIF-1α, SDF-1, and CXCR4 in each group of mice was detected by PCR. Results Compared with the control group, changes in indicators in model A mice did not meet the POI modeling standard. The ovarian index, uterine index, and body weight of mice in the B model group were decreased significantly (P<0. 01) , the weight of the C model group was decreased significantly (P<0. 01) , and the ovarian index of the D model group was decreased significantly (P<0. 05) . Serum contents of FSH and LH in B, C, and D model groups were increased (P<0. 05, P<0. 01) , the E2, PROG, AMH, INH-B, and T contents were decreased ( P < 0. 01) . The numbers of basal follicles, pre-sinus follicles, sinusoidal follicles, antral follicles, preovulatory follicles, and corpus luteum were decreased significantly (P<0. 05, P<0. 01) and the number of atresia follicles was increased significantly (P<0. 01) in B, C, and D model groups. The apoptotic area of TUNEL staining in A, B, C, and D model groups was increased significantly (P<0. 05, P<0. 01) . Expression of CD34, VEGFA, and EPO in B, C, and D model groups was decreased significantly (P<0. 05, P < 0. 01) . mRNA expression of HIF-1α, SDF-1, and CXCR4 in A and B model groups was significantly increased (P<0. 05, P< 0. 01) . Compared with the B model group, the relevant indexes of C and D model groups were changed significantly, indicating that C and D models were more serious and tended to develop POF. Conclusions The B model group is the turning point of ovarian function from impaired POI to irreversible POF, suggesting that 3 days of administrating Tripterygium wilfordii polyglycoside is optimal to induce a POI disease model for effective drug intervention.