PURPOSE: Dexamethasone is frequently administered to prevent or treat chronic lung disease in human neonates who are also prone to hypoxic-ischemic(HI) insults. Recently, meta-analysis of the follow-up studies reveals a significantly increased odd ratio for the occurrence of cerebral palsy or an abnormal neurologic outcome, and there is conflicting evidence regarding the impact of dexamethasone exposure on HI brain injury. This study was conducted to explore the effect of post-HI dexamethasone administration on neuronal injury in neonatal rats. METHODS: HI was produced in seven-day-old rats by right carotid artery ligation followed by two hours of 8% oxygen exposure. At the end of HI, the animals were injected intraperitoneally either with dexamethasone(0.5 mg/kg) or saline. Neuronal injury was assessed seven days after the HI by the area of infarction, TUNEL reactivity, Bcl-2 and Bax expression in brain. RESULTS: Post-insult dexamethasone administration resulted in reduction of weight gain and a higher mortality rate during seven days after HI. Dexamethasone treatment revealed no effect on the size of brain infarction induced by HI. Bax protein expression increased in dexamethasone treated brain but Bcl-2 protein expression and TUNEL reactivity revealed no significant differences between dexamethasone treated and non treated brain. Increased Bax protein expression suggest upregulation of the apoptosis by dexamethasone. CONCLUSION: The result suggests the adverse role of Post-HI administration of dexamethasone in neonatal HI.