Stroke-induced brain injury has been viewed mainly from a neurocentric perspective, with much attention given to the primary injury site and its penumbra. However, an important notion derived from recent studies, including our own, favor a view that the peripheral inflammatory state influences the outcome of primary injury. We investigate the mechanism(s) by which peripheral immunity may be regulated by cerebral ischemia and how this contributes to CNS damage in stroke. Despite a well-documented role of CD36 in the pathogenesis of other conditions such as atherosclerosis, inflammation, and lipid metabolism, its role in cerebral ischemic injury had not been delineated. We believe that our report on CD36 is the first study that demonstrates the role of this receptor in inflammation and brain injury in ischemic stroke. As CD36 is expressed in many different tissues and cell types, including peripheral monocytes/macrophages, our studies focus on the effect of CD36 expressed in the peripheral organs including bone marrow, spleen and blood. Major findings from these studies are the recognition of peripheral immunity on CNS injury, validating CD36 as a target in acute pathology, and characterizing a pharmacological agent that inhibits CD36 pathways. This ongoing project is to identify novel molecular targets that may serve as possible therapeutic strategies to attenuate acute stroke pathology.