Ischemic stroke, particularly permanent occlusion, accounts for the overwhelming majority of all strokes. In addition to the occlusion of arteries, the inflammatory response plays a pivotal role in the severity of the cerebral injury and its clinical prognosis. Here, panax notoginseng saponins (PNS) extracted from a traditional Chinese herbal medicine was administered following permanent middle cerebral artery occlusion (MCAO) in rats to explore the neuroprotective mechanisms against ischemic injury. The results showed that MCAO surgery was successful in producing an infarct and that PNS and nimodipine could ameliorate the neurological deficits. The expression levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) were increased, while the level of interleukin-10 (IL-10) was reduced in the infarct cortex 7 days after MCAO, as assessed by immunohistochemistry, western blotting and quantitative real-time PCR (qRT-PCR). PNS was able to markedly reduce the overexpression of IL-1 beta and TNF-alpha while significantly promoting the expression of IL-10, but did not affect the elevated expression of TGF-beta 1. Meanwhile, nimodipine was able to significantly reduce the expression of IL-1 beta and TNF-alpha, but had no obvious effect on IL-10 or TGF-beta 1. In addition, the serum levels of TNF-alpha, IL-10 and TGF-beta 1 were basically consistent with cerebral tissue results; however, the IL-1 beta levels did not differ. We conclude that PNS can directly down-regulate the overexpression of proinflammatory factors IL-1 beta and TNF-alpha while up-regulating the expression of anti-inflammatory factor IL-10 in the core region of the cerebral infarct, thereby preventing neurological damage in rats after permanent MCAO.