Ghrelin is a brain-gut peptide and exerts a broad range of biological actions including anti-apoptosis.Our previous works have shown that ghrelin inhibited neuronal apoptosis in middle cerebral artery occlusion (MCAO) and cultured neurons via up-regulated the expression of HSP70.Here we study the molecular and signal transduction mechanisms of ghrelin up-regulated HSP70.The apoptosis model was made by oxygen and glucose deprivation (OGD) in cultured cortical neuron.We found that ghrelin prevented cortical neuron apoptosis from ODG and unregulated the Heat shock factor protein 1(HSF1).Also found the expression of HSF1 was increased by ghrelin, but inhibited by the blocker of ERK1/2 pathway, PD98059 and blocker of AKT pathway, LY294002.Also found that LY294002 decreased the ERK1/2 phosphorylation, however, the AKT phosphorylation did not reduced by PD98059.Above results indicated that ghrelin inhibited OGD-induced neuronal apoptosis in cultured neuron by increased the expression of HSF1 and HSP70 via AKT and ERK1/2 pathway.