Bone morphogenetic protein (BMP)‐7 mediated neuroprotective effect of cerebral ischemic preconditioning (IPC) has been studied in ischemic animal model, but the underlying cellular mechanisms have not been clearly clarified. In this study, primary cortical neurons and SH‐SY5Y cell line were used to investigate the role of BMP‐7 and its downstream signals in the neuroprotective effects of oxygen‐glucose deprivation preconditioning (OGDPC). Immunocytochemistry was used to detect the expression of neurofilament in neurons. MTT and lactate dehydrogenase activity assay were used to measure the cytotoxicity. Western blot was used to detect the protein expression of BMP‐7 and downstream signals. BMP inhibitor, mitogen‐activated protein kinase inhibitors, Smad inhibitor and siRNA of Smad 1 were used to investigate the role of corresponding signaling pathways in the OGDPC. Results showed that OGDPC‐induced overexpression of BMP‐7 in primary cortical neurons and SH‐SY5Y cells. Both of endogenous and exogenous BMP‐7 could replicate the neuroprotective effects seen in OGDPC pretreatment. In addition, extracellular regulated protein kinases, p38 and Smad signaling pathway were found to be involved in the neuroprotective effects mediated by OGDPC via BMP‐7. This study primarily reveals the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. This article is protected by copyright. All rights reserved.