The most important final target of treatment during post-cardiac arrest care after cardiac arrest is recovery of brain function. Therapeutic hypothermia is known as the only treatment that can help to recover brain function during post-cardiac arrest care. Among the ovarian hormones, progesterone had been known as a substance that has the effects in patients with traumatic, ischemic and hemorrhagic brain injury. We want to evaluate the effect of progesterone in rat receiving progesterone treatment during post-cardiac arrest care after asphyxia cardiac arrest. Rat cardiac arrest was induced via asphyxia. All male rats were maintained for seven minutes of no flow time, and then cardiopulomonary resustation was started. All rats were randomly divided progesterone and control group. We performed post-cardiac arrest care of rats after retrun of spontaneous circulation (ROSC). All rats were given 0 or 16 mg/kg injections of progesterone at 1, 24 and 48 h after ROSC. We checked the neuro-deficit score (NDS) at 24 and 48 h after ROSC. Also, we assayed aquaporin-4 (AQP4) using western blot analysis, and DNA fragmentation of hippocampal damage were assessed by the TUNEL method at 72 h. There was no significant change NDS in both group. But progesterone treatments significantly reduced AQP4 expression in the tissue bounded by the hippocampal areas compared to control group (p < 0.001). Also progesterone treatment significantly reduced the number of TUNEL-positive cells in CA1 in comparison with control rats. There were significant reduction of AQP4 expression and TUNEL-positive cells in progesterone treated rat during post-cardiac arrest care after 7 minute asphyxia cardiac arrest.