Objective: To investigate the role and mechanism of IQ motif containing GTPase activating protein 1 (IQGAP1) in oxygen-glucose deprivation/reoxygenation (OGD/R) -induced polarization of BV-2 microglia cells . Methods: The IQGAP1 overexpression plasmid ( oe-IQGAP1 ) and its negative control plasmid ( Vector) were transfected into BV-2 cells , and then the polarization of BV-2 cells was induced by OGD/R , and exogenous inter- feron-γ(IFN-γ) recombinant protein was used for intervention . Cell proliferation rate was detected by cell counting kit-8 (CCK-8) assay. The level of lactate dehydrogenase (LDH) in the supernatant was detected using a test kit. The mRNA expression levels of IQGAP1 , IFN-γand microglial polarization markers inducible nitric oxide synthase (iNOS) , CD86 , CD206 and arginase1 (Arg1) were detected by quantitative real-time polymerase chain reaction (RT-qPCR) . The levels of IFN-γ, tumor necrosis factor-α(TNF-α) , interleukin (IL)-1β, IL-4 and IL-10 in the cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA) . The protein expression levels of IQGAP1 and IFN-γwere detected by Western blot. Results: Following OGD/R treatment , the proliferation rate of BV-2 cells , the levels of IL-4 and IL-10 in the supernatant , and the mRNA expression levels of CD206 and Arg1 were significantly reduced (all P < 0. 05) . In contrast , the levels of LDH , TNF-αand IL-1βin the supernatant , as well as the mRNA expression levels of iNOS and CD86 in the cells significantly increased (all P < 0. 05) . More- over , both the mRNA and protein expression levels of IQGAP1 in the cells significantly decreased ( P < 0. 05) . Following IQGAP1 overexpression , the levels of IL-4 and IL-10 in the supernatant of BV-2 cells , along with the mRNA expression levels of CD206 and Arg1 in the cells , were significantly elevated under OGD/R conditions (all P < 0. 05) . Meanwhile , the levels of TNF-αand IL-1βin the supernatant and the mRNA expression levels of iNOS and CD86 in the cells significantly decreased (all P < 0. 05) . Additionally , both the intracellular expression and secretion of IFN-γprotein were reduced ( all P < 0. 05) , whereas the mRNA expression of IFN-γremained un- changed . However , combined intervention with exogenous IFN-γrecombinant protein obviously reversed the inhibi- tory effect of IQGAP1 overexpression on OGD/R-induced M1 polarization of microglia. Conclusion IQGAP1 over- expression inhibits M1 polarization of microglia under OGD/R conditions through the suppression of IFN-γexpres- sion and secretion .