Objective To investigate the protective effect of Tanshinone ⅡA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. Methods The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 μg/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA. In TSA 0 (also called OGD group), 0.5, 1.0, 2.0 μg/mL groups, expression levels of NLRP3 and caspase-1 were detected by Western blot, while IL-1β and IL-18 in culture medium of those groups were detected by ELISA assay. Results The highest expression level of NLRP3 came to 12 h of reperfusion. The maximum effective concentration of TSA was 2.0 μg/mL. The expression levels of NLRP3, caspase-1, IL-1β and IL-18 decreased with the increase of TSA concentration. Conclusion TSA can inhibit the expression of protein and cytokines of NLRP3 inflammatory signaling pathway in OGD/R BV-2 cells, which may be one of the molecular mechanisms of the protective effect of TSA on OGD/R cells.