Interleukin-6 (IL-6) is a proinflammatory cytokine that decisively induces the development of insulin resistance and pathogenesis of type 2 diabetes mellitus (T2DM) through the generation of inflammation by controlling differentiation, migration, proliferation, and cell apoptosis. The presence of IL-6 in tissues is a normal consequence, but its irregular production and long-term exposure leads to the development of inflammation, which induces insulin resistance and overt T2DM. There is a mechanistic relationship between the stimulation of IL-6 and insulin resistance. IL-6 causes insulin resistance by impairing the phosphorylation of insulin receptor and insulin receptor substrate-1 by inducing the expression of SOCS-3, a potential inhibitor of insulin signaling. In this article, we have briefly described how IL-6 induces the insulin resistance and pathogenesis of T2DM. The prevention of inflammatory disorders by blocking IL-6 and IL-6 signaling may be an effective strategy for the treatment of insulin resistance and T2DM.