Objective To investigate the protection of agmatine on blood brain barrier (BBB) permeability and the effect on the expression of aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) in ischemic reperfusion injury rats.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into normal control group (NC),model group and agmatine group,and there were 20 rats in each group.Normal control group was treated with intraperitoneal injection of saline in 2 hours after incision and suture of skin.Model group was treated with intraperitoneal injection of saline in 2 hours after the establishment of middle cerebral artery occulation (MCAO) model.Agmatine group was treated with intraperitoneal injection of agmatine (AGM) in 2 hours after the establishment of MCAO model.The damage of blood brain barrier was detected by measuring the permeability of blood brain barrier.The infarct size of brain was observed with TTC staining.The morphological changes of neurons were observed with electron microscope.The expressions of AQP4 and MMP9 were detected using immunohistochemical method.Results The permeability of BBB of agmatine treatment group (0.31±0.10) decreased significantly compared with the model group (0.46±0.09) (P＜0.05),but was still significantly higher than the normal control group (0.24±0.12) (P＜0.05).There was no infarction area in normal control group and the infarction areas of agmatine group decreased obviously compared with the model group.Compared with model group,the number of neurons with morphological changes reduced significantly and the degree of pathological changes of neurons was obviously improved in agmatine group.Compared with normal control group,the expression of AQP4 and MMP9 in ischemic penumbra of left cerebral hemisphere parietal cortex in the rats of model group and agmatine group increased significantly(P＜0.05).And the expression of AQP4 and MMP9 in model group was significantly higher than that of agmatine group(P＜0.05).Conclusion Agmatine has a protective effect on BBB with ischemia-reperfusion injury due to its down-regulation the expression of AQP-4 and MMP-9.