The aim of present study was to determine the effect of estrogen treatment on blood-brain barrier permeability in rats with induced global cerebral ischemia. The study included six-month-old female Sprague-Dawley rats which were divided into the following groups: Control-Ischemia-Reperfusion (C + I-R); Ovariectomy-Ischemia-Reperfusion (Ovx + I-R); Ovariectomy + Estrogen + Ischemia-Reperfusion (Ovx + E + I-R); Ovariectomy + Ischemia-Reperfusion + Estrogen (Ovx + I-R + E). Ischemia-reperfusion was induced by clamping two carotid arteries, then opening the clamp. Blood-brain barrier permeability was visualized by Evans Blue extravasation and quantified by spectrophotometry. Our results indicate that following ischemia-reperfusion the BBB permeability is increased in ovariectomized rats (Evans Blue extravasation) compared to the control group in the cortex, thalamus, hippocampus, cerebellum and brain stem, while in the midbrain no significant increase was detected. In contrast, BBB permeability in the groups treated with estrogen, administered either before or after ischemia-reperfusion, was significantly lower than in ovariectomized animals. In conclusion, the increase in BBB permeability resulting from experimentally induced cerebral ischemia was prevented by exogenous estrogen treatment. The study results indicate that estrogen may be used for therapeutic purposes in ischemia-reperfusion.