The purpose of the present study was to explore the combination effect of FTY720 and vitamin E on cerebral ischemia. Astrocytes were isolated from newborn Sprague‑Dawley rats and were subjected to FTY720, vitamin E, or combination of the two. The astrocyte cultures were then exposed to oxygen‑glucose deprivation (OGD) to simulate an ischemic model in vitro. Cell viability, lactate dehydrogenase (LDH) leakage and cell apoptosis were detected following 12 h of exposure to OGD. In addition, the levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β, total antioxidant capacity, intercellular adhesion molecule (ICAM)‑1, vascular cell adhesion molecule (VCAM)‑1, chemokine (C‑X‑C motif) ligand (CXCL)‑10, heme oxygenase (HO)‑1 and superoxide dismutase (SOD)‑1 were measured. Pre‑treatment with FTY720 or vitamin E significantly elevated the cell viability and decreased LDH release and number of apoptotic cells. Combination treatment with FTY720 and vitamin E demonstrated a synergistic protective effect on OGD‑induced cell viability, toxicity and apoptosis. Pre‑treatment with FTY720 markedly reduced the release of IL‑1β, TNF‑α, IL‑6, ICAM‑1, VCAM‑1 and CXCL‑10, and pre‑treatment with vitamin E increased the levels of antioxidant, HO‑1 and SOD‑1. However, pre‑treatment with FTY720 combined with vitamin E revealed a synergistic effect. Pre‑treatment with FTY720 combined with vitamin E exerts synergistic neuroprotective effects in the simulated cerebral ischemia in vitro.