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．