Background and Purpose: Ischemic stroke is a complex neurological diseases with limited therapeutic approaches. Baicalin-Liquiritin (BA-LI) are effective components isolated from Scutellariae radix and Glycyrrhiza glabra which possesses antioxidant and anti-inflammatory properties. However, whether BA-LI has beneficial effects on ischemic stroke as well as its underlying mechanism remains to be elucidated. Experimental Approach: In order to investigate the protective effect of BA-LI on ischemic stroke and its molecular mechanism, we constructed an in vitro oxygen glucose deprivation/re-oxygenation (OGD/R) model as well as the middle cerebral artery occlusion (MCAO/R) model and detected the relevant indexes and the expression of Keap1-Nrf2/HO-1 signaling pathways related proteins. Results: BA-LI could effectively reduce the volume of cerebral infarction in MCAO/R mice, activate Keap/Nrf2 signaling, and the expression of anti-inflammatory factors TGF-β1 and IL-10 was elevated after administration of BA-LI, and BA-LI had a protective effect on cerebral ischemia/reperfusion injury in mice; in vitro OGD/R model was constructed by using BV2 cells, and 5uM BA-LI was able to significantly increase cell viability and down regulate Keap protein expression, upregulated Nrf2 and HO-1 protein expression, and increased the levels of M1 and M2 inflammatory factors IL-1β and TNF-α. Conclusion: BA-LI attenuates cerebral ischemia reperfusion injury via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ischemic stroke. Key Words: Ischemic stroke, Cerebral Ischemia Reperfusion Injury，Baicalin, Liquiritin, Keap1-Nrf2/HO-1 signaling pathways