Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury (CIRI). The exact mechanisms underlying I/R injury are unclear. In this study, we aimed to determine the role of m 6 A-modified methylase complex methyltransferase-like 3 (METTL3) in cerebral ischemiareperfusion (I/R) injury. We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar (MA-C) and the brain of middle cerebral artery occlusion (MCAO) model mice. METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation, which increased with METTL3 over-expression. Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis, which was significantly reduced with METTL3 up-regulation. In an MCAO model, METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis, indicating that METTL3 OE treatment could ameliorate brain edema and injury. Thus, METTL3 could be used as a target to treat I/R injury.