Abstract: 【ABSTRACT】Objective: To investigate the neuroprotective effects of the Ginkgolides Injection (GIs) against ischemic stroke-induced injury and further explore the possible mechanisms concerned. Methods: The modified method of Zea Longa was used to establish the transient middle cerebral artery occlusion (tMCAO) model in rats. GIs was injected intraperitoneally (ip, bid, 3d) to rats 1h after onset of reperfusion with different doses (1.25, 2.5 and 5mg/kg). The neurological deficits were assessed in each group after cerebral ischemia. Brain water content was measured by wet/dry weight method and Infarct volume was observed by TTC staining. Western Blot was used to evaluate the expression level of protein related to ER stress and autophagy in penumbra region of rats treated with GIs (2.5mg/kg) at 24h and 72h after reperfusion. Results: GIs (2.5 and 5mg/kg) treatment significantly reduced neurological deficits, water content, and cerebral infarct volume after stroke. GIs (2.5mg/kg) treatment protected against ischemia/reperfusion-induced ER stress and autophagy. Conclusions: GIs are neuroprotective against ischemic brain injury through the down regulation of ER stress and autophagy.