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Purpose: To study the anti-hypoxia effects of ginseng oligopeptides (GOPs) in mice. Methods: Mice were randomly assigned to six groups: vehicle control group, whey protein-fed group (0.30 g/kg body weight, BW), and four groups given GOP at doses of 0.075, 0.150, 0.300, 0.600 g/kg BW. All treatments were administered via gavage once a day for a total of 30 days. Results: GOPs significantly extended survival times under normobaric hypoxia, sodium nitrite toxicosis and acute cerebral ischemia. Moreover, GOPs enhanced the levels of RBC, Hb and Hct; decreased brain malonaldehyde (MDA) and lactate contents, enhanced brain lactate dehydrogenase (LDH) activity, and upregulated the mRNA expression levels of hypoxia-inducible factor 1alpha (HIF1α) and vascular endothelial growth factor (VEGF). Conclusion: GOPs exert anti-hypoxia effects via mechanisms which may involve improvement of oxygen-carrying capacity of blood and oxygen utilization, reduction of lipid peroxidation-associated lesions, enhancement of brain capacity to buffer against lactic acidosis, promotion of angiogenesis, and regulation of response to hypoxia.