Abstract: Objective：To explore the protection of hyperbaric oxygen (HBO) preconditioning on blood-brain barrier of plateau hypoxia in Rats. Methods：SD rats were randomly divided into three groups including normal control group (group A), high altitude hypoxia group (group B) and HBO preconditioning treatment of high altitude hypoxia group (group C), by tail vein injection of 2% Evans blue (EB), and by fluorescence microscopy to observe brain EB spot, we evaluated the changes of BBB permeability by detecting the contents of EB and water in brain tissue through UV spectrophotometer and dry wet weight method, respectively. Results：The number of red spots, EB content and brain water content of brain tissues in group A were significantly lower than those in group B and group C (P<0.001). The number of red spots, EB content and brain water content in group B were significantly higher than those in group C (P<0.001). Conclusions：HBO pretreatment can significantly reduce the increase of BBB permeability caused by high altitude hypoxia, and has obvious protective effect on the damage of BBB caused by high altitude hypoxia.