Emerging studies have shown that circRNA catenin beta 1 (circCTNNB1) plays a critical role in cancer. However, the expression and function of circCTNNB1 in cerebral ischemia/reperfusion injury (IRI) have not been reported. In this study, we found that circCTNNB1 and scavenger receptor class B type 1 (SRB1) expression levels were significantly down-regulated in oxygen glucose deprivation and reperfusion (OGD/R)-treated mice astrocyte (mAS), while similar results were also observed in mice middle cerebral artery occlusion (MCAO) model. Moreover, overexpression of circCTNNB1 alleviated cell apoptosis, oxidative stress and inflammatory response induced by OGD/R in vitro. In addition, up-regulation of circCTNNB1 increased SRB1 expression level to protect damage of mAS cells from OGD/R. Both circCTNNB1 and SRB1 could interact with miR-96-5p, and overexpression of miR-96-5p could efficiently reverse the function of circCTNNB1 on OGD/R-treated mAS cells. Finally, the circCTNNB1 protected against cerebral ischemia-reperfusion injury via positive regulating SRB1 in vivo. In summary, our results suggested that circCTNNB1 may function as a competing endogenous RNA for miR-96-5p to ameliorate cerebral IRI, possibly providing novel evidence that circCTNNB1 and SRB1 may serve as biomarker of and therapeutic target for cerebral IRI.