Objective:To study the roles of ClC-3 chloride channel played in the microglial phenotypic transformation induced by oxygen-glucose deprivation. Methods:Microglia(BV-2 cell line) was applied to establish the oxygen-glucose deprivation (OGD) model,and then respectively pretreated with different concentrations of chloride channel blockers,including DIDS and NPPB. Cell damage and the effective concentration of drugs were determined by MTT activity. The mRNA level of cell phenotypic factors,such as M1 markers including tumor necrosis factor -琢(TNF--琢),interleukin 1-茁(IL-1-茁)and CD86,M2 markers containing transforming growth factor -茁(TGF--茁) and cell surface molecule CD206 were detected by real-time fluorescent quantitative PCR. Expression of ClC-3 was downregulated by small RNA interference,and then pretreated with chloride channels blockers-DIDS and NPPB. Finally,the effects of blockers were observed by the MTT activity. Results:Pretreatment with DIDS (1,10 μmol/L) and NPPB(1 μmol/L) could partially reverse the decrease of BV-2 cells viability induced by OGD. DIDS(1 μmol/L) and NPPB (1 μmol/L) pretreatment could reduce the mRNA level of TNF--琢,IL-1-茁 and CD86,they could also promote expression of TGF--茁 mRNA. However,the reversal effect of DIDS and NPPB could be abolished by the down-regulation of ClC-3 expression. Conclusion:ClC-3 chloride channel is essential for the phenotypic transformation of microglia caused by OGD. Blocking ClC-3 chloride channel could inhibit its transformation into M1 phenotype.