Objective:This study aims to observe the intervention effect of rapamycin on ovarian dysfunction caused by maternal obesity and evaluate the safety of drugs. Methods:A female obesity mice model with high fat diet was established and then randomly divided into the treatment group injected with rapamycin and the control group injected with PBS. After 24 weeks,the number of ovulations was counted and the oocytes were collected for spindle operation. Immunofluorescence staining was used to evaluate the effect of rapamycin on ovulation function and oocyte quality in obese mice,and the expression of ovarian-related genes in protein and mRNA was detected by Western blot and RT-qPCR. Results:The weight of ovarian in rapamycin treated mice decreased. Expression of phosphorylated ribosoma lprotein(P-rps6) and the phosphorylated 4E binding protein1P(P-4EBP1) was significantly decreased in rapamycin-treated obese mice,and the number of superoved oocytes increased compared with the control. But results of the oocyte spindle staining showed no significant difference in oocyte quality between two groups. The mRNA expression level of tumor necrosis factor-α(TNF-α) in the ovary was increased after rapamycin treatment. There were no significant changes in serum estrogen and follicle stimulating hormone between two groups. Conclusion:Rapamycin has a tendency to improve ovulation function by inhibiting the mTOR signaling pathway. It was not found that rapamycin had a significant effect on oocyte quality. This study provided experimental basis for research of rapamycin on fertility in obese women in the future.