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Background andPurpose—Cerebral ischemia initiates cascades of pathological events such as edema, blood-brain barrier breakdown, and tissue degeneration.Thrombolytic therapy is useful to treat those diseases, but it was followed by ischemia and reperfusion injury(IRI).Limb remote ischemic postconditioning(LRIP) can be used to reduce IRI, but it s mechanisms arent clear.We ratiocinate LRIPreduces IRI by reversingeNOS uncoupling.Methods—Focal ischemia was induced in adult Sprague-Dawley rats by middle cerebral artery occlusionfor 2 hours followed by 24 hours reperfusion.Before this surgery, we gave folic acid (FA) to drug treatment group by garage.After 2 hours ischemia, LRIP group and LRIP+FA group were treated with LRIP.After 24 hours reperfusion, behavioral testing, vascular function, NO concentration, SOD activity in the serum and the infarct size of brain were detected.The mRNA of eNOS, GTPCH, P22phox and xanthine oxidase (X O) in the ischemic region were detected by RT-PCR,nitrotyrosine (Tyr-NO2) was detected by Western blot.Results—LRIP and FA could significantly improve forelimb placing; LRIP, FA and LRIP+FA could ameliorate the tail hang of IRI model; The expression of eNOS mRNA increased in FA and FA +LRIP group; But the expression ofX O and P22phox mRNA decreased in LRIP, FA and FA+ LRIP groups;GTPCH expression increased in LRIP, FA and FA + LRIP groups.Conclusions—when the brain experiences ischemia and reperfusion, eNOS is uncoupling in the ischemic region.LRIP can mitigate IRI by reducing eNOSuncoupling.