〔Abstract〕 Objective To investigate the regulatory effect of corticosterone(CORT) pretreatment on the activation of microglia by lipopolysaccharide(LPS) and the inhibitory effect of Biochanin A(Bio A) on microglia activation.Methods The MTT method was used to select the optimal concentrations for LPS,CORT and Bio A on BV2 cells;BV2 cells were divided into 5 groups: Control group,CORT(50 nmol/L) group,LPS(1 μg/mL) group,LPS(1μg/mL) + CORT(50 nmol/L) group,and LPS(1 μg/mL) + CORT(50 nmol/L) + Bio A(5 μmol/L) group;Except for the control group,each group was first incubated with CORT(50 nmol/L) for 2 h,and then each group was co-incubated with the corresponding concentrations of LPS(1 μg/mL) and Bio A(5 μmol/L) for 36 h;DCFH-DA probe method was used to detect reactive oxygen species(ROS) content; Western blot was used to detect the protein expression levels of inflammatory cytokines,5-hydroxytryptamine(5-HTT),glucocorticoid receptor(GR),mineralocorticoid receptor(MR),NOD-like receptor family pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC) and cysteine-aspartic protease 1(Caspase-1). Results Compared with the CORT(50 nmol/L) and LPS(1 μg/mL) groups,cells in the CORT(50 nmol/L) + LPS(1 μg/mL) group showed increased cell viability,higher levels of ROS,and increased levels of inflammatory cytokines,NLRP3,ASC,and Caspase-1 protein expression( P＜0. 05 ) ．Conclusion A low dose of CORT pretreatment reinforces LPS- induced BV2 cell activation; Bio A inhibits CORT-pretreated LPS-induced BV2 cell activation．The mechanism of which may be related to the inhibition of NLRP3 inflammasome activation．