Inflammatory damage plays a pivotal role in cerebral ischemia and may represent a target for treatment. Pigment epithelium-derived factor (PEDF) is proven to possess neuroprotective property. But there is little known about the intrinsic PEDF after cerebral ischemia. This study evaluated the time course expression of the intrinsic PEDF and its underlying regulation mechanisms after cerebral ischemia. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion. Telmisartan (PPARgamma agonist) and GW9662 (PPARgamma antagonist) were systemically administered to explore the effect on PPARgamma, PEDF, NF-kappaB and MMP-9 expression at 24 h after cerebral ischemia by western blot and qRT-PCR. The neurological deficits, brain water content and infarct volume were measured. Compared with normal group, the expressions of PEDF and PPARgamma decreased, and the expression of NF-kappaB and MMP-9 increased at early stage after ischemia (P < 0.05). Compared with the vehicle group, the decrease of PEDF and PPARgamma was significantly up-regulated and the increase of NF-kappaB and MMP-9 was down-regulated by telmisartan at 24 h (P < 0.05). The neurological deficits, brain water content and infarct volume were dramatically alleviated by telmisartan (P < 0.05). Telmisartan's effects were reversed by GW9662 co-administration (P < 0.05). The expression of intrinsic PEDF was down-regulated at the early stage of cerebral ischemia. The protective effects of intrinsic PEDF by activating PPARgamma pathway may be one of the strategic targets for cerebral ischemic therapies.