Upregulation of AT1R in the acute setting is associated with cardioprotection from ischemia reperfusion injury, whereas AT2R is associated with increased myocardial injury. Activation of AT1R promotes cell hypertrophy and proliferation, while activation of AT2R counteracts AT1R-mediated effects and induces apoptosis. The Cefsulodin sodium expression of AT1R and AT2R are regulated by glucocorticoids. Several GREs have been identified in rat AT1aR and AT2R promoters. Stimulation of GREs on AT1aR promoter increases gene activity while GREs at AT2R represses promoter activity. The effect of glucocorticoids on the expression profile of ATRs in the heart and cardiac recovery from ischemic reperfusion insult is not clear. The present study tests the hypothesis that dexamethasone treatment protects rat heart function from global ischemia and reperfusion injury and that the mechanism of this protection involves GR-mediated fine-tuning of ATR expression patterns in the heart. Herein we present evidence that dexamethasone induces the protection in rat hearts from ischemia/ Drospirenone reperfusion-mediated injury associated with increasing the expression of AT1R and decreasing AT2R. We further demonstrate that dexamethasone regulates ATR expression and protects the heart through a GR dependent mechanism. This is the first study to our knowledge revealing that short-term in vivo treatment with dexamethasone reduced AT2R and increased AT1R expression in the heart, which contributed to the cardioprotective effects of glucocorticoids in a setting of acute ischemia and reperfusion injury. The dexamethasone-mediated regulation of ATR expression and cardioprotection were through a GR dependent mechanism by increasing the binding of GR to GRE sites at both AT1aR and AT2R promoters. The present study demonstrated that intraperitoneal injection of 1 mg/kg/day dexamethasone for 5 days reduced myocardial injury and improved functional recovery in a setting of acute ischemia and reperfusion insults.Based on body surface area, the dose of dexamethasone used in the present study is well within the dose range used in humans. This effect was blocked by a GR antagonist RU486 and, thus indicated a GR-dependent mechanism.