Objective：To observe the effect of Xingnaojing on inflammatory cytokines in brain tissues in heatstroke-induced rats, and to explore the mechanism of cognitive improvement. Methods: Thirty-six Wistar rats were randomly divided into control group, model group, and Xingnaojing group. The rats were intervened with high temperature of (41±0.5) ℃ and high humidity of (75%±5%). The core temperature of the rats was monitored, when the temperature reach to 42 ℃ , the rats were treated with cooling administration, and the Xingnaojing group were administrated with drugs i.v. After 3 days of continuous intervention, water maze tests were performed, and then brains were taken for the expression of inflammatory cytokines and related proteins dectection. Results: The results of the study showed that Xingnaojing had a significant protective effect on cognitive dysfunction in heatstroke-induced rats. The intervention of Xingnaojing significantly reduced the expression of inflammatory cytokines in the rat brain,inhibited the activation of microglia in the brain, and improved neuronal apoptosis in the hippocampal CA1 area. In addition, Xingnaojing significantly reversed the increased expression of TLR4 protein, increased NF-κB phosphorylation and increased NLRP3 protein expression in the rat brain caused by heatstroke. Conclusion: Xingnaojing can improve cognitive dysfunction by suppressing the inflammatory response in the brain of heatstroke disease.