Objective To investigate the effect of glaucocalyxin A(GLA)on neuroinflammation and the HMGB1-RAGE signaling pathway in rats with Alzheimer disease(AD).Methods Rats were given intracerebroventricular injec-tion of Aβ1-42 solution to establish a model of AD,and then the rats were randomly divided into sham-operation group,model group,donepezil group,low-dose GLA group and high-dose GLA group,and high GLA+HMGB1 group,with 15 rats in each group.The Morris water maze test was used to assess the learning and memory abilities of rats;HE staining was used to observe the pathological and morphological changes of hippocampal tissue;ELISA was used to measure the lev-els of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in hippocampal tissue;immu-nofluorescence assay was used to measure the expression of the microglia marker protein Iba-1 and the astrocyte marker protein GFAP;Western blotting was used to measure the expression of HMGB1-RAGE pathway-related proteins in hippo-campal tissue.Results Compared with the sham-operation group,the model group had significant increases in escape la-tency,the content of TNF-α/IL-6/IL-1β,the positive expression area of Iba-1 and GFAP proteins,and the expression lev-els of HMGB1,RAGE,TLR4,and p-NF-κB p65/NF-κB p65(P<0.05),as well as significant reductions in the time spent in the target quadrant and the number of platform crossings(P<0.05).Compared with the model group,the low-and high-dose GLA groups had significant reductions in escape latency,the content of TNF-α/IL-6/IL-1β,the positive ex-pression area of Iba-1 and GFAP proteins,and the expression levels of HMGB1,RAGE,TLR4,and p-NF-κB p65/NF-κB p65(P<0.05),as well as significant increases in the time spent in the target quadrant and the number of platform crossings(P<0.05),and there were no significant differences between the high-dose GLA group and the donepezil group(P>0.05).Further supplementation experiments using HMGB1 recombinant protein showed that the inhibitory effect of GLA on neuroinflammation was reversed,with a sig-nificant increase in the level of RAGE(P<0.05).Conclusion GLA can alleviate neuroinflammation in AD rats by inhibiting the HMGB1-RAGE signaling pathway.