Introduction: Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α2-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigated whether dexmedetomidine induces cardioprotection against myocardial apoptosis injury. Methods: In order to assess the role of dexmedetomidine on myocardial apoptosis, we established a grave scalding rat model. Blood and myocardial tissue from the ventriculus sinister were harvested, then troponin, myocardial apoptosis, and expression of caspase-12, GRP78, and CHOP were assessed. Results: Dexmedetomidine significantly reduced myocardial apoptosis, improved functional recovery, and reversed myocardial injury induced by grave scalding. The heart rate in the five groups studied was significantly different (p < 0.05). The number of buffy-stained nucleoli in the myocardial cell was highest in the simple scald group. The expression of caspase-12 obviously increased in the simple scald group. The expression of GRP78 and CHOP increased in the simple scald and scald and 50 μg/kg dexmedetomidine groups (p < 0.05). Conclusions: The results show that dexmedetomidine (DEX) produces cardioprotection against myocardial apoptosis injury. DEX is not only a useful sedative, but also plays a pivotal role in anesthetic cardioprotection. The potential benefits of DEX protection in high risk cardiovascular patients undergoing surgery are enormous.