Objective: To investigate the effect of excelluar signal-regulated kinase(ERK) on rat hippocampal neurons with oxygen-glucose deprivation(OGD). Methods:Cultured hippocampal neurons were designed into four groups:normal group,OGD group, PD98059 10 μmol/L and 30 μmol/L groups. The apoptosis of neurons was determined by flow cytometry, and Western blot was used to evaluate protein expression of ERK1/2 and pERK1/2. Results:Compared with normal control group, neuron apoptosis increased while pERK1/2 protein expression decreased obviously in OGD group(both P < 0.01). Neuron apoptosis increased and pERK1/2 protein expression decreased more significantly in PD98059 groups compared with OGD group(both P < 0.01). Changes in 30 μmol/L PD98059 group were more significant than 10 μmol/L PD98059 group (P < 0.01). Each group showed no significant change in ERK expression(P > 0.05). Conclusion:ERK may be involved in neuronal apoptosis after OGD, and inhibition of ERK pathway can promote neuronal apoptosis.