Objective To explore the possible mechanism of the treatment of ovarian reserve dysfunction with modified Guishen Pills（归肾丸）. Methods A total of 90 female ICR mice were randomly divided into a blank control group

a model group

a estradiol group and modified Guishen Pills low

medium and high dose group

with 15 in each group. Except for blank control group

mice were intraperitoneally injected with ethylene dioxide cyclohexene solution 160 mg/（kg·d） for 15 consecutive days to establish model of decreased ovarian reserve function. After successful modeling

the Guishen Pills high-dose

medium-dose and low-dose groups were administrated with modified Guishen Pills suspension 57.0

28.5 and 14.3 g/（kg·d）

respectively; the estradiol group was administrated with estradiol valerate 0.15 mg/（kg·d）; the blank control group and the model group were administrated with normal saline 0.1 ml/10 g each day and all mice were invented for 30 days. HE dyeing was used to observe ovarian tissue pathology morphology

and enzyme-linked immunoassay method was used to detect serum follicle stimulating hormone（FSH）

luteinizing hormone（LH）

estradiol（E

2

）

muller tube hormone（AMH） level. Western Blot method was used to detect phosphatidyl inositol 3 kinase（PI3 K）

protein kinase B（AKT）

mammals rapamycin target protein（mTOR） protein expression in ovarian tissue of mice. Results Pathological results showed that compared with the blank group

the number of primordial follicles

presinus follicles and sinusoid follicles in the model group decreased significantly

the number of atretic follicles increased significantly

and the number of luteum was rare. The number of follicles was more abundant in the estradiol group and the high-dose group of Guishen Pills

in which many luteums can be seen. In modified Guishen Pills middle and low dose groups

atretic follicles were dominant with a small amount of corpus luteum. Compared with the blank control group

serum FSH and LH in the model group were significantly increased

AMH and E2 were significantly decreased

and the protein contents of PI3 K

AKT and mTOR in ovarian tissues were all decreased（P

<

0.05 or P

<

0.01）. Compared with the model group

serum FSH and LH were significantly reduced

AMH was significantly increased

and PI3 K and AKT proteins in ovarian tissues were significantly increased in the Guishen Pills middle and high dose groups and estradiol groups（P

<

0.05 or P

<

0.01）. There was no significant difference between the Guishen Pills high dose group and the estradiol group in all indexes（P

>

0.05）. Conclusion The modified Guishen Pills may improve ovarian function by affecting the PI3 K/AKT/mTOR signaling pathway in ovarian tissues

and the effect is better at a high dose.