〔Abstract〕 Objective To observe the effect of hypoxia on pituitary adrenal axis in rats and the therapeutic effect of Gynostemma pentaphyllum saponins(GPs)intervention. Methods 50 male SD rats were randomly divided into normoxia control group, hypoxia control group, and hypoxia + GPs low, medium, and high dose intervention groups, with 10 rats in each group. Rats in the normoxia group were kept in a normoxia animal room for 28 days, while rats in the hypoxia group and drug intervention group were kept in a low-pressure oxygen chamber for 28 days. Among them, hypoxia+GPs low, medium and high dose groups of rats were gavaged daily with GPs of 40 mg/kg, 80 mg/kg, and 160 mg/kg, respectively. After 28 days, rats were killed in batches, their body weight and pituitary weight were measured, and pituitary index was calculated; HE staining method was used to observe the morphology and structure of rat pituitary gland; immunohistochemical and Western blot methods were used to observe the expression level of pituitary adrenocorticotropin(ACTH)protein in rats; ELISA method was used to observe serum ACTH and corticosterone(CORT)concentrations in rats. Results Hypoxia had no significant effect on pituitary gland morphology and quality in rats. Hypoxia might induce the expression of rat pituitary ACTH protein and an increase in serum ACTH and CORT concentrations, while GPs might reduce the expression of rat pituitary ACTH protein and serum ACTH and CORT concentrations induced by hypoxia. Conclusion GPs have a significant effect on the pituitary adrenal axis induced by hypoxia in rats, and there is a dose-effect relationship between GPs and effect.