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Agmatine, an analog of L-arginine, is an endogenous substance synthesized by arginine decarboxylase, which has been shown to possess neuroprotective effects following brain ischemia.Nitric oxide is generated by sequential oxidation of the guanidinium group in L-arginine, and agmatine might protect the brain from ischemic injury by interfering with nitric oxide signaling. This study investigated the effects of agmatine on cerebral cortex neuronal injury following transient global cerebral ischemia and also detected nitric oxide synthase expression and peroxynitrite formation.Results demonstrated that intrapentoneal injection of agmatine in global cerebral ischemia/reperfusion alleviated ischemia/reperfusion-induced cerebral cortical cortex neuronal injury and cellular apoptosis,decreased neuronal and inducible nitric oxide synthase expression at 24, 48, and 72 hours following global cerebral ischemia and reperfusion, and greatly inhibited nitrotyrosine levels, which reflect the amount of peroxynitrite formed. These findings indicated that agmatine alleviates cerebral cortex neuronal injury following global cerebral ischemia and decreases nitric oxide synthase expression and peroxynitrite formation following ischemia/reperfusion.