〔Abstract〕 Objective To investigate the protective effects and mechanism of isoliquiritigenin(ISL) on the brain inflammation with traumatic brain injury(TBI) in rats.Methods TBI model was established with the modified Feeney's method,and adult male SD rats were randomly subjected to either sham operation,model or ISL(15,30,60 mg/kg) group,with 10 rats in each group. Two hours after operation,ISL group was given intraperitoneal injection once,sham operation group and model group were given intraperitoneal injection of equal volume normal saline for 7 days,once a day. 7 days after the TBI,the neurobehavior of rats in each group was evaluated,then the rats were sacrificed to measure the brain water content and inflammatory factors. In addition,the protein and mRNA changes of Toll-like receptor 4( TLR4)-TANK-binding kinase( TBK1)-IκB kinase ε( IKKε) signaling pathway in the brain tissue were also examined. Results ISL improved the neuroethology of TBI rats,reduced the brain water content and expression of inflammatory factors,and inhibited TLR4-TBK1-IKKε signal pathway,with significant difference. Conclusion The protective effects of ISL on the rats with inflammation after TBI may be related to the inhibition of TLR4-TBK1-IKKε signal pathway.