Nogo-A, a myelin-associated neurite outgrowth inhibitory protein, binds with the Ng-R receptor to activate RhoA intracellular signals and inhibit the plasticity after CNS injury. We evaluated the effect of hyperbaric oxygen (HBO) on the expression of Nogo-A, Ng-R, and RhoA after transient global ischemia in a rat 2 vessel occlusion global ischemic model. Male SD rats (n=78) were randomly divided into 13 groups: 1 sham group, 6 groups of global ischemia, and 6 groups of HBO treatment after global ischemia. HBO (3ATA) was applied for 2 hr at 1 hr after global ischemia. Rats were sacrificed at 6, 12, 24, 48, and 96 hr and 7 days. Global ischemia (10 min) produced a marked increase of Nogo-A/B, Nogo-A, Ng-R, and RhoA expression. Immunohistochemistry showed increased Nogo-A/B and Nogo-A located in the myelin sheath of ischemic brain cortex. Ng-R expressed on the surface of neurons and their processes, and RhoA expressed inside the cytoplasm of neurons in ischemic brain. HBO significantly reduced neurological injury, decreased the levels of Nogo-A, Ng-R, and RhoA in ischemic injured cortex (p<0.05).