Objective: To investigate whether ellagic acid(EA) exerts a protective effect on ischaemic brain injury by regulating the miR-18a/thrombospondin-1(TSP-1) axis. Methods: Ischemic brain injury was simulated using rat brain microvascular endothelial cells(RBMECs) oxygen-glucose deprivation(OGD) model and rat middle cerebral artery occlusion(MCAO) model. Apoptosis and apoptosis-related proteins in RBMECs were assessed via TUNEL staining, flow cytometry, and Western blotting(WB). The proliferation, migration, and tubulogenesis capabilities of RBMECs were assessed using EdU, Transwell, and tube formation assays; MicroRNA microarray analysis was employed to detect differentially expressed microRNAs in brain tissue from MCAO rats following EA intervention, with validation via real-time quantitative polymerase chain reaction(qRT-PCR). Bioinformatics prediction of miR-18a's action pathways was corroborated through WB, dual luciferase reporter assays, and rescue experiments. Results: Compared with the OGD group, the EA intervention group showed reduced apoptosis, increased proliferation and migration, and a higher number of tube formations in RBMECs. In MCAO rats, EA pretreatment markedly improved Longa scores, alleviated brain tissue pathological damage, and reduced neuronal apoptosis. MicroRNA microarray analysis revealed that miR-18a exhibited the most significant differential expression in ischaemic brain tissue following EA intervention compared to controls. qRT-PCR results demonstrated markedly elevated miR-18a expression in RBMECs after EA treatment. Bioinformatics prediction identified TSP-1 as a direct target of miR-18a. Western blotting confirmed that transfection with miR-18a mimic significantly downregulated TSP-1 expression in RBMECs. Dual luciferase reporter assays validated TSP-1 as a direct target of miR-18a. Rescue experiments demonstrated that inhibiting miR-18a reversed EA ' s aforementioned protective effects on RBMECs. Conclusion: EA exerts anti-apoptotic and pro-angiogenic effects by modulating the miR-18a/TSP-1 signalling axis, thereby mitigating ischaemic brain injury. This axis may represent a potential therapeutic target for post-stroke neuroprotection.