Objective: To investigate whether post-treatment of cultured astrocytes with 14,15-epoxyeicosatrienoic acids（14,15-EET）would increase the brain derived neurotrophic factor（BDNF）secretion after oxygen-glucose deprivation and reperfusion（OGD/R）, and if this effect would subsequently protect neurons during reperfusion after OGD in the co-cultured system. Methods: Astrocytes and neurons were subjected to OGD/R. Exogenous 14,15-EET were applied to astrocytes in the reperfusion period and ELISA was then performed to measure BDNF secretion from astrocytes at different time points following OGD/R. After that，the OGD neurons were co-cultured with the astrocytes that were previously incubated with DMSO or 14,15-EET.Tunnel staining was used to detect neuronal apoptosis. Results: BDNF secretion was significantly promoted by application of 14,15-EET on astrocytes in the reperfusion stage after OGD. Exposure of OGD neurons to astrocyte media previously conditioned with 14,15-EET reduced the neuronal apoptosis，but the pro-survival effect could be partly reversed by TrkB inhibitor k252a. Conclusion Exogenous administration of 14,15-EET augments BDNF secretion from astrocytes，which increases TrkB receptor occupancy on neurons and promotes neuronal survival after OGD/R.