Objective:To explore the mRNA expression of EphA5 receptor in hippocampus of neonatal rat with hypoxic-ischemic encephalopathy (HIE) as well as the relationship with apoptosis of neurons. Methods:Seven-day-old SD rats were randomly divided into HIE group,HIE+ EphA5-Fc group and control group . The mRNA expression of EphA5 receptor and the apoptosis of neurons in hippocampus of neonatal rats in 3 groups were determined by qRT-PCR and TUNEL staining. Results:①The mRNA expression of EphA5 receptor in HIE group increased and peaked at 12h,which was still higher than that in control group at 48 h (P < 0.05). Compared with HIE group,the mRNA expression of EphA5 receptor decreased in HIE+ EphA5-Fc group (P < 0.05),which recovered to that in control group (P > 0.05). ②In HIE group,apoptosis of hippocampus neurons increased after 6 h,and peaked at 24 h. Apoptosis of hippocampus neurons in HIE+ EphA5-Fc group was remarkably lower than that in HIE group (P < 0.05). Conclusion:The up-regulation of EphA5 receptor and apoptosis of hippocampus neurons could be suppressed by inhibitor of EphA5 receptor,which suggests the activity of EphA5 receptor may be one of the mechanisms of brain damage by hypoxic-ischemic.