Objective:To investigate whether quercetin reduces neuroinflammation in epileptic rats by regulating high mobility group protein B1(HMGB1),receptor for advanced glycation end products(RAGE)and nuclear factor kappa-B(NF-κB),and to explore the possibility of HMGB1/RAGE/NF-κB pathway as a new target of quercetin.Methods:Twelve SD rats were randomly selected from 60 SD rats as healthy group,and the remaining rats were used to construct experimental models of epilepsy rats.Rats that were successfully modeled were divided into model group,high-dose quercetin group,low-dose quercetin group,quercetin+pathway activator group,with 12 rats in each group.Pathological changes of hippocampal tissue of rats were observed;neurobehavioral function of rats was evaluated;levels of tumor necrosis factor-α(TNF-α),IL-6 and IL-1β,and mRNA and protein expression levels of HMGB1,RAGE,NF-κB in hippocampal tissue of rats were detected.Results:Structure of hippocampus of rats in healthy group was complete;compared with healthy group,structure of hippocampal tissue of rats in model group was scattered,the number of surviving neurons was observably reduced,apoptotic index was observably increased,the Racine grade was observably increased,TNF-α,IL-1β,IL-6 contents and mRNA and protein expression levels of HMGB1,RAGE,NF-κB in hippocampal tissue were significantly increased;com-pared with model group,structure of hippocampal tissue of rats in low-and high-dose quercetin groups was relatively complete,the number of surviving neurons was observably increased,apoptotic index was observably decreased,the Racine grade was significantly decreased,TNF-α,IL-1β,IL-6 contents and mRNA and protein expression levels of HMGB1,RAGE,NF-κB were significantly re-duced,and the improvement effect of high-dose quercetin group was better;compared with high-dose quercetin group,the number of surviving neurons in quercetin+pathway activator group was significantly reduced,apoptotic index was significantly increased,the Ra-cine grade was significantly increased,TNF-α,IL-1β,IL-6 contents and mRNA and protein expression levels of HMGB1,RAGE,NF-κB in hippocampal tissue were significantly increased.Conclusion:Quercetin can effectively reduce neuroinflammation in epilep-tic rats by inhibiting the HMGB1/RAGE/NF-κB pathway and reducing the mRNA and protein expressions of related genes.