Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/reperfusion injury,protecting injured neural cells.However,hyperbaric oxygen may aggravate oxidative stress.By contrast,normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic/hypoxic disease.Rats inhaled normobaric oxygen(95%O2)for 6 consecutive days,and then a rat model of focal cerebral ischemia was established.Nissl and 2,3,5-triphenyltetrazolium chloride(TTC)staining revealed that normobaric oxygen pretreatment improved neurological deficits and reduced infarct volume.Immunohistochemical staining and western blot assay revealed that the expression of hypoxia-inducible factor-1α,Notch-1,vascular endothelial growth factor and erythropoietin were increased.Behavioral studies also verified that neurological deficit scores increased.The hypoxia-inducible factor inhibitor 2-methoxyestradiol treatment at 1 hour before administration of normobaric oxygen could suppress the protective effect of normobaric oxygen.Given these observations,normobaric oxygen pretreatment may alleviate cerebral ischemic injury via the hypoxia-inducible factor signal pathway. Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia / reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxidative stress. By contrast, normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic / hypoxic disease. Rats inhaled normobaric oxygen (95% O2) for 6 consecutive days, and then a rat model of focal cerebral ischemia was established. Nissl and 2,3,5-triphenyltetrazolium chloride (TTC) pretreatment improved neurological deficits and reduced infarct volume. Immunohistochemical staining and western blot assay revealed that the expression of hypoxia-inducible factor-la, Notch-1, vascular endothelial growth factor and erythropoietin were increased. Behavioral studies also verified that neurological deficit scores increased. The hypoxia-inducible factor inhibitor 2-methoxyestradiol treatment at 1 hour before administration of normo baric oxygen could suppress the protective effect of normobaric oxygen. Given these observations, normobaric oxygen pretreatment may alleviate cerebral ischemic injury via the hypoxia-inducible factor signal pathway.