The purpose of the study is to investigate the anti-inflammatory and analgesic activity of Zanthoxylum armatum water extract (ZWE) and mechanism of action. To establish a glial cell lipopolysaccharide-stimulated model,with celecoxib as positive control,and to observe the reversal effect of different doses of ZWE.Establishment of mice planta pain inflammation model by injection of complete Freund’s adjuvant in Kunming mice.Sixty female Kunming mice were selected and randomly divided into six groups,including blank control grou,model control group,positive control group and low(25 mg/kg),medium(50 mg/kg) and high dose groups(100 mg/kg) of ZWE.Determination of mechanical pain thresholds in mice by Von Frey filaments;ELISA was used to determine changes of the levels of inflammatory cytokines (TNF-α,IL-1β and β-EP) in the serum of mice;Pathological changes in the planta of mice observed by HE staining;HE staining was used to observe the changes of heart,liver,spleen,lung and kidney tissues in mice;Changes in the expression of CD11b,CD45 and NeuN proteins in mice spinal cord observed by immunofluorescence assay.The results showed compared with the model group,ZWE improved thesurvival rate of glial cells in vitro (P<0.05);Von Frey tests indicated that different doses of ZWE increased mechanical pain thresholds in inflammatory mice (P<0.001);ELISA results showed that ZWE decreased the levels of pro-inflammatory cytokines TNF-α and IL-1β and increased the expression level of anti-inflammatory cytokines β-EP in mice serum (P<0.001);Expression of CD11b and CD45 in mice spinal cord was reduced by ZWE.Meanwhile,NeuN,a neuronal nuclear protein,showed its expression was decreased by immunofluorescence results,revealing that the anti-inflammatory effect of ZWE is involved in the regulation of the nervous system.These data indicated ZWE showed resistance to inflammatory cells,increased the pain tolerance threshold in inflammatory tissues of mice,and this effect was associated with its modulation of TNF-α, IL-1β and β-EP levels and inhibition of the expression of the related proteins CD11b,CD45 and NeuN in the inflammatory pathway.