Our results indicate that the involvement of hyperglycemia-induced oxidative stress and impaired PI3K/Akt and JAK2/STAT3 signaling in compromising the cardioprotection of RPC and suppressing oxidative stress with NAC may attenuate myocardial I/R injury and preserve RPC-induced cardioprotection by restoring PI3K/Akt and JAK2/STAT3 signaling in diabetes. This evidence concerns the gene JAK2 and Hyperglycemia.