Cerebral ischemia is a neurovascular disease in which blood flow to the brain decreases which leads to glucose and oxygen deprivation in the brain and this finally results in neuronal cell death. On the other hand, it was found that reperfusion augments this damage by increasing availability of oxygen. Cerebral ischemia can be classified into two major categories as focal and global cerebral ischemia. The mechanisms of neural cell damage following cerebral ischemia reperfusion is complex cascade, which ultimately leads to cell apoptosis or necrosis following disturbance in ion distribution, excitotoxicity, oxidative stress, and, mitochondrial dysfunction. The incidence of stroke is higher in postmenopausal women than premenopausal ones and it was found that they suffer from more severe side effects than men in matched age. It was found that estrogen has neuroprotective actions against cerebral ischemia in both male and ovariectomized rats via various mechanisms as antioxidant, anti-inflammatory, nootropic, and glucose transporters enhancing beside activation of survival signal transduction pathway either genomic or non-genomic.