In this study, the effects of progesterone (P 4 ) on the immunoreactivity to the neurite growth inhibitor Nogo-A, its receptor (Ng-R), and its effector Rho-A in the rat hippocampus, in association with parameters of spatial learning and memory following global cerebral ischemia, were assessed. Adult male rats were subjected to global cerebral ischemia (15min), and treated with P 4 or its vehicle at 15min, 2, 6, 24, 48 and 72h of reperfusion. Immunoreactivity to Nogo-A, Ng-R, and Rho-A was evaluated at 24h, 72h or 7d, or at 14d of reperfusion after rats were tested in the Morris Water Maze (MWM). Global cerebral ischemia induced an increase in Nogo-A, Ng-R, and Rho-A immunoreactivities in the cell bodies of CA1 pyramidal neurons at 24h after global cerebral ischemia, peaking at 72h, and persisting 14d later. In addition, at 72h, a strong immunoreactivity was observed in the hippocampal layers where dendritic arborizations of CA1 pyramidal neurons are located. Treatment with P 4 reduced Nogo-A, Ng-R, and Rho-A immunoreactivities in CA1, particularly at 72h of reperfusion. These effects of P 4 were consistent with the parameters of a more efficient spatial learning and memory in the MWM, as compared to vehicle-treated rats. Overall results suggest the reduction of neurite growth inhibitory molecules Nogo-A, Ng-R, and Rho-A, as a part of the restorative effects of progesterone possibly allowing the plastic phenomena to occur, able to support the functional preservation of the hippocampus following global cerebral ischemia.