BackgroundIschemic cerebrovascular disease (ICVD) is one of three fatal diseases in humans, along with heart disease and malignant tumors. Cerebral ischemia/reperfusion injury (CI/RI) is the primary cause of ICVD. Recently, seipin was reported to be crucial for lipid droplet formation, hepatic steatosis, and axonal atrophy. However, the function and mechanism of seipin in CI/RI has not been explicitly stated.MethodsOxygen–glucose deprivation/reoxygenation (OGD/R) hippocampal neuron cell line (HT‐22) and middle cerebral artery occlusion (MCAO) in rats were established. The levels of apoptosis‐ and autophagy‐related proteins and seipin were confirmed by western blot. Cell proliferation was assessed with CCK‐8, and ischemic infarction and pathological structure were monitored by TTC and H&E staining, and tissue apoptosis was assessed through TUNEL assay.ResultsThe proliferative activity was decreased, and apoptosis and autophagy pathways could also be induced in the OGD/R HT‐22 cells. Seipin overexpression accelerated viability and inhibited apoptosis and autophagy in the OGD/R HT‐22 cells. Moreover, the data revealed that seipin overexpression could also attenuate cerebral infarction, apoptosis. Autophagy pathways could be repressed by seipin in the MCAO rats.ConclusionSeipin has a protective role against CI/RI in rats, and its mechanism might be relevant to the suppression of apoptosis and autophagy, suggesting that seipin might be a latent target for CI/RI.