Abstract :Each year about 795,000 Americans will suffer a new or recurrent stroke which remains as one of the leading causes of mortality, morbidity and disability in USA. The treatment goal of acute ischemic stroke is relieving the arterial occlusion (recanalization) and restoring cerebral blood flow (reperfusion) as soon as possible. Indeed, shorten the time from symptom onset to thrombolytic therapy and applying endovascular clot retrieval can achieve excellent reperfusion for most patients. The successes of these emerging therapies open the opportunity to treat is chemia/reperfusion (I/R) injury for improving outcomes after acute ischemic stroke.Toll-like receptor (TLR) mediated innate immune and inflammatory responses play a central role in cerebral I/Rinjury. We have found that activation of TLR3 or TLR9 by theiragonists protect the brain fromI/Rinjury.Drugs that can be given locally during reperfusion to reduce I/Rinjury, to provide neuroprotection, and to salvage the tissue at risk may provide invaluable information for treatment and management of stroke patients.