To evaluate the effects of Guizhi Fuling Pills(GZFP)on uterine fibroids in rats，and to observe its effect on uterine histopathology and PI3K-AKT signaling pathway.Methods:A total of 90 female SD rats were randomly divided into a blank group，a model group and a Chinese medicine group，with 30 rats in each group.Rats in the model group and the Chinese medicine group were intraperitoneally injected with estradiol benzoate to simulate uterine leiomyoma model.Rats in blank group were injected intraperitoneally with the same dose of normal saline.Rats in the Chinese medicine group were given GZFP intragastric administration after successful modeling.Rats in the blank group and the model group were given the same dose of normal saline intragastric administration once a day，for continuous 18 d.The changes of uterine wet weight，uterine coefficient and thickness of uterine smooth muscle layer were compared in each group.The pathological changes of uterine tissues were compared by Masson staining.The concentrations of PI3K，AKT and p-AKT in uterine tissues were detected by Western blotting.The estrogen receptor(ER)and progesterone receptor(PR)were detected by immunohistochemistry.Results: 1)Compared with the blank group，the wet weight of uterus，the coefficient of uterus and the thickness of smooth muscle layer of uterus in the model group and the Chinese medicine group were significantly increased，and the above indexes in the Chinese medicine group were significantly lower than those in the model group.The difference was statistically significant(P<005). 2)Masson staining showed that in the blank control group，uterus tissue slices were red and few.In the model group，a large number of dark blue fibrous tissue could be seen in the uterine circular and longitudinal muscles，and even some of the myometrial groups had obvious lumpy fibrous structure. 3)Compared with the blank group，the concentrations of PI3K and p-AKT in the uterus of the model group and the Chinese medicine group were up-regulated.There was no significant difference in the concentrations of T-AKT among the three groups(P>005).The concentrations of PI3K and p-AKT in the Chinese medicine group were significantly lower than those in the model group(P<005). 4)Compared with the blank group，the positive expression rate of ER and PR in uterine smooth muscle of the model group and the Chinese medicine group increased，and the expression rate of ER and PR in the Chinese medicine group was lower than that in the model group.The difference was statistically significant(P<005).Conclusion:GZFP can significantly inhibit the occurrence and development of uterine leiomyoma，and its mechanism may be mediated by PI3K-AKT signaling pathway progesterone/estrogen receptor.