The major findings of this study are as follows: 1) ACh- and flow-induced endothelium-dependent vasodilation was impaired in coronary arterioles of diabetic mice, and was mediated by IL-6 and TNF-α signaling; 2) Interactions between IL-6 and TNF-α determined the mRNA and protein expression levels for both IL-6 and TNF-α contributing to coronary endothelial dysfunction in T2D; and 3) Coronary endothelial dysfunction in T2D was regulated by IL-6 through increased production of superoxide and subsequent reduction in p-eNOS. The gene discussed is IL6; the disease is type 2 diabetes mellitus.