OBJECTIVE：To stu dy the effect of psoralen on osteoporosis in postmenopausal rats and PI3K/Akt/mTOR signaling pathway. METHODS ：Totally 60 healthy female SD rats were randomly divided into normal group ，model group ，positive control group（0.09 mg/kg estradiol ），psoralen low-dose ，medium-dose and high-dose groups （22，44，88 mg/kg），with 10 rats in each group. Except for normal group ，the other groups were ovariectomized to establish Postmenopausal osteoporosis model. After 2 months of normal feeding after operation ，normal group and model group were given the constant volume of normal saline intragastrically，and administration groups were given the corresponding solution intragastrically ；the volume was 0.005 mL/g， once a day ，for consecutive 98 days. 24 h after last administration ，the BMD of femur and vertebra of right lower extremities in rats was determined. The contents of serum calcium ，osteocalcin and P1NP，the serum levels of BMP2 and VEGF were determined；mRNA and protein expression of PI3K，Akt and mTOR in femur tissue were detected.RESULTS ：Compared with normal group ，BMD of femur and vertebra ，serum contents of calcium ，osteocalcin，P1NP and serum levels of BMP 2，VEGF in model group were decreased significantly ，while the mRNA and protein expression of PI 3K，Akt and mTOR were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ，BMD of femur and vertebra ，serum levels of calcium ， osteocalcin，P1NP and serum levels of BMP2（except for psoralen medium-dose group ），VEGF（except for psoralen medium-dose group）were increased significantly in psoralen medium-dose and high-dose groups ，positive control group ，while the mRNA expression（except for psoralen low-dose group ）and protein expression of PI 3K，Akt and mTOR in administration groups were decreased significantly （P＜0.05 or P＜0.01）；BMD of femur ，serum levels of calcium ，BMP2 and PI 3K protein expression in psoralen high-dose group were significantly higher than positive control group （P＜0.05），and mTOR mRNA expression in psoralen high-dose group was significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Psoralen can improve osteoporosis in postmenopausal rats ，the mechanism of which may b e associated with inhibiting PI 3K/Akt/mTOR signaling pathway.