Abstract: 【Objective】 This study aimed to investigate the potential ameliorative effects of HyPericum Perforatum L. extract（HPE） on liver and kidney injury in acute hypoxia rats.【Method】 The anti-hypoxic active components of HPE,including 20% ethanol extract,70% ethanol extract,and 95% ethanol extract,were initially screened using a normobaric hypoxia model in mice. Subsequently,a hypobaric hypoxia injury model was established using 80 rats. The rats were randomly divided into various groups: normoxia control group（NG）,hypoxia model group（HG）,HPE low,medium,and high dose groups（HPE-L,HPE-M,HPEH,100,200,400 mg/kg）,hyperoside low and high dose groups（HYP-L,HYP-H,50,100 mg/kg）,and dexamethasone group（DXM,4 mg/kg）. The effects of HPE on the histopathological changes of the liver and kidney in acute hypoxia rats were observed,and related inflammatory factors and oxidative stress indexes were measured.【Result】 Compared with the model group,rats treated with HPE showed decreased levels of malondialdehyde（MDA） and hydrogen peroxide（H2O2）（P＜0. 01,P＜0. 05）,and increased levels of glutathione（GSH）,total superoxide dismutase（T-SOD）,and catalase（CAT） activities（P＜0. 01,P＜0. 05）. Furthermore,the release of inflammatory factors interleukin-1β（IL-1β）,interleukin-6（IL-6）,tumor necrosis factor-α（TNF-α）,and vascular endothelial growth factor（VEGF） was inhibited in rats treated with HPE（P＜0. 01,P＜0. 05）.【Conclusion】 HPE demonstrated a certain degree of ameliorative effect on liver and kidney injury in rats with acute hypoxia.