Abstract: Existing experimental evidence suggests that PPARγ may play a beneficial role in neuroprotection from various brain pathologies. Here we found that focal cerebral ischemia induced by middle cerebral/common carotid arteries occlusion (MCA/CCAo) induced up-regulation of PPARγ messenger RNA in the ischemic hemisphere as early as 6 h after the ischemic event. The increased PPARγ mRNA expression was primarily associated with neurons in the ischemic penumbra, suggesting an important role for PPARγ in neurons after ischemia. Intraventricular injection of 15d-Δ12,14-prostaglandin J2 (15d-PGJ2), a proposed endogenous PPARγ agonist, into the ischemic rat brains significantly increased the PPARγ-DNA-binding activity and reduced infarction volume at 24 h after reperfusion. We propose that PPARγ up-regulation in response to ischemia may contribute to PPARγ activation in the presence of PPARγ agonists. Activation of PPARγ in neurons at an early stage after ischemia may represent a pro-survival mechanism against ischemic injury. [Copyright &y& Elsevier]