Objective The changes of relevant indexes in the mice model of early-onset ovarian insufficiency caused by tripterygium wilfordii polyglycoside were discussed, and the best time point for intervention was determined. Methods Forty female ICR mice were randomly divided into blank group, A, B, C, and D model groups, with 8 mice in each group. The blank group was given gavage purified water for 14d (0.01ml/10g), and the remaining groups were given tripterygium wilfordii polyglycoside suspension (80mg/kg, 0.01ml/10g) for 1d (A model group), 3d (B model group), 7d (C model group), 14d (D model group), and the materials were taken in batches. Weigh the body weight, wet weight uterus and bilateral ovaries of mice in each group; Serum FSH, LH, E2, P, AMH, INH-B and T contents were detected by enzyme-linked immunoassay. HE staining observed the number and development status of follicles and corpus luteum at all levels of mice in each group. TUNEL fluorescence staining method detected the apoptosis area in the ovaries of mice in each group. The IHC method detected the positive expression of VEGFA, CD34 and EPO proteins in the ovaries of mice in each group. The mRNA expression of HIF-1α, SDF-1 and CXCR4 in each group of mice was detected by PCR. Results Compared with the blank group, the changes of indicators in model A did not meet the POI modeling standard. The ovarian index, uterine index and body weight of mice in the B model group decreased significantly (P<0.01), the weight of the C model group decreased significantly (P<0.01), and the ovarian index of the D model group decreased significantly (P<0.05). The serum indexes of the B, C and D model groups increased the contents of FSH and LH (P<0.01 or P<0.05), and the contents of E2, PROG, AMH, INH-B and T decreased (P<0.01). The number of basal follicles, presinus follicles, sinusoidal follicles, antral follicles, preovulatory follicles and corpus luteum decreased significantly (P<0.01 or P<0.05) and the number of atresia follicles increased significantly (P<0.01) in the B, C and D model groups. The apoptosis area of TUNEL fluorescent staining in A, B, C, and D model groups increased significantly (P<0.01 or P<0.05). The positive expression of CD34, VEGFA and EPO in the B, C and D model groups decreased significantly (P<0.01 or P<0.05). The expression of mRNA in the A and B model groups of HIF-1α, SDF-1 and CXCR4 was significantly increased (P<0.01 or P<0.05). Compared with the B model group, the relevant indexes of the C and D model groups changed significantly, indicating that the C and D models were more serious and tended to develop POF. Conclusion The B model group is the turning point of ovarian function from impaired POI to irreversible POF, suggesting that 3d administration of tripterygium wilfordii polyglycoside is the best time to induce POI disease model and effective drug intervention.