The expressions of GRP78, p60 ATF-6, CHOP, and cleaved caspase-12 were all increased in the myocardial tissue of diabetic rats and high glucose (HG)-induced H9C2 cells, while exogenous H2S abolished these changes, suggesting that the hyperglycemia-induced ER stress of cardiomyocytes was inhibited by exogenous H2S. Moreover, exogenous H2S and NAC (ROS scavenger) notably decreased HG-induced intracellular ROS levels in H9C2 cells. Here, CASP12 is linked to Hyperglycemia.