Objective To evaluate the effect of ulinastatin on the expression of aquaporin-4 (AQP4) during focal cerebral ischemia-reperfusion (I/R) in rats.Methods One hundred and thirty-five male adult SpragueDawley rats,weighing 230-280 g,were randomly divided into 3 groups (n =45 each):sham operation group (S group),I/R group and ulinastatin group (group U).The rats were anesthetized with intraperitoneal 10％ chloral hydrate 3.5 ml/kg.Focal cerebral ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 repeffusion.In U group,ulinastatin 100000 U/kg was injected immediately after beginning of reperfusion,while the equal volume of normal saline was injected in S and I/R groups.The rats were sacrificed at 6,24 and 48 h of repeffusion and brains were removed for determination of infract volume (by TTC),brain water content and expression of AQP4 (by immunohistochemistry) in brain tissues.Results Compared with S group,the infarct volume and brain water content were significantly increased,and the expression of AQP4 was up-regulated at each time point in I/R and U groups (P ＜ 0.05).Compared with I/R group,the infarct volume and brain water content were significantly decreased,and the expression of AQP4 was down-regulated at each time point in U group (P ＜0.05).Conclusion The mechanism by which ulinastatin mitigates focal cerebral I/R injury is related to down-regulation of AQP4 expression in brain tissues.