Objective To explore the role of CTSB (cathepsin B)-mediated NLRP3 bodies in arsenic-induced inflammatory activation of mouse microglial BV-2 cell.Methods BV-2 cells in logarithmic growth phase were respectively exposed to NaAsO₂ solution at the final concentration of 0, 2, 4 and 8 μmol/L for 24 h. Cell viability was detected by CCK-8 assay. The levels of intracellular CTSB, NLRP3, Caspase-1, IL-18, and IL-1β were determined by Western blot. The intracellular lysosome level was detected by flow cytometry analysis. According to the experimental results, CTSB inhibitor group (5 μmol/L CA074-Me+8 μmol/L NaAsO₂,10 μmol/LCA074-Me+8 μmol/L NaAsO₂) was added to detect the expression of NLRP3, Caspase-1, IL-1β and IL-18 in the two groups.Results Compared with the control group, the cell inhibition rate of all exposed groups increased in a dose-dependent manner, the level of lysosome integrity decreased, the difference was statistically significant (P<0.01). The expression of CTSB, NLRP3, IL-1β and IL-18, Caspase-1 increased significantly, the difference was statistically significant (P<0.01). Compared with the inhibitor group, the intracellular CTSB, NLRP3, IL-1β and IL-18, Caspase-1 levels of BV-2 cells exposed to 8 μmol/L NaAsO₂ without inhibitor were significantly higher (P<0.01).Conclusion NaAsO₂ can induce the increase of CTSB level in microglia, mediate the activation of microglia by NLRP3 inflammatory bodies, promote the release of inflammatory factors and damage the central nervous system.