ObjectiveTo explore the effect and regulatory mechanism of notoginseng total saponins on apoptosis of mammary gland cells in rats with mammary gland hyperplasia. MethodSixty female non-pregnant SD rats were randomly divided into control group， model group， Notoginseng total saponins low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） groups and tamoxifen group （1.8 mg·kg^-1）， 10 rats per group. Rat model of mammary gland hyperplasia was established by intramuscular injection of estradiol benzoate and progesterone. Oral administration was performed according to the experimental dose of each group， once a day for 30 consecutive days. The rats in the control group and the model group were given equal volume of normal saline by gavage every day. After administration， the diameter of the second pair of nipples of the rats was measured with vernier calipers， and breast tissue samples were collected and stained with hematoxylin and eosin （HE） to observe the pathological changes. Immunohistochemistry was used to determine the expression of apoptosis regulators B-cell lymphoma-2 （Bcl-2）-associated X （Bax） and Bcl-2， and Western blot was conducted to detect the expression of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway-related proteins. ResultCompared with the control group， the model group had increased diameter of the second pair of nipples （P<0.05）， elevated volume of mammary lobules and number of acinus， diffuse mammary gland hyperplasia， and up-regulated expression of Bcl-2 protein， increased ratio of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR （P<0.05） and decreased expression of Bax in the mammary gland （P<0.05）. Compared with the conditions in the model group， the diameter of the second pair of nipples of the rats in the notoginseng total saponins low-， medium- and high-dose groups and tamoxifen group was decreased （P<0.05）， and the number of mammary lobules and acinus and the amount of secretions were reduced. In addition， the mammary gland hyperplasia was alleviated， and a decrease was observed in the expression of Bcl-2 protein and the ratio of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR （P<0.05）， and an increase in the expression of Bax （P<0.05）. ConclusionNotoginseng total saponins could improve mammary gland hyperplasia in rats， and its mechanism was related to regulating PI3K/Akt/mTOR pathway and promoting apoptosis of mammary gland cells.