Abstract： Objective To investigate the effect of progesterone on expressions of tight junction proteins zonula occludens-1 (ZO-1) and occludin, and permeability of blood-brain barrier (BBB) in rats after focal cerebral ischemia-reperfusion (IR). Methods A total of 42 healthy male SD rats were randomly divided into sham-operated group (n=6) and IR group; IR group was further divided into 6subgroups according to different time points ofreperfusion (3, 6, 12, 24, 48 and 72 h of reperfusion, n=6).The models of focal cerebral IR injury were induced by middle cerebral artery occlusion. To observe the permeability of BBB, Evans blue (EB) extravasation was surveyed by the means of EB fluorescentquantitation; Western blotting was used to detect the expressions of ZO-1 and occludin.Progesterone-treated group and vehicle control group (n=6) were established at the time point of the peak level of permeability of BBB; the effect of progesterone on the expressions of ZO-1 and occludin, and BBB permeability was investigated and compare with those in the IR group.Results At 3 h of reperfusion after cerebral ischemia for 2 h, the permeability of BBB began to increase, reaching its peak level at 24 h of reperfusion. The expressions of ZO-1 and occludin began to decrease at 3 h of reperfusion, reaching their lowest levels at 24 h of reperfusion. The amount of EB in the progesterone-treated group was significantly less than that of corresponding IR sub-group (P≤0.05); the expressions of ZO-1 and occludin in progesterone-treated group were increased significantly as compared with those in corresponding IR sub-group (P≤0.05).Conclusion Progesterone could reduce the permeability of BBB by decreasing the expressions of ZO-l and oecludin.