Diabetes is a complex disease that affects many organs directly or indirectly. Type 2 diabetes mellitus is characterized by insulin resistance with a relative deficiency in insulin secretion. It has become apparent that inter‐organ communication is of great importance in the pathophysiology of diabetes. Far from being an inert tissue in terms of inter‐organ communication, it is now recognized that skeletal muscle can secrete so‐called myokines that can impact on the function of distant organs/tissues both favourably and unfavourably. We have proposed that communication between insulin‐resistant skeletal muscle and β‐cells occurs in diabetes. This is a novel route of communication that we further suggest is modified by the prevailing degree of insulin resistance of skeletal muscle. This review focuses on the various myokines [interleukin‐6 (IL‐6), tumor necrosis factor‐α, CXCL10, follistatin and IL‐8] which have been identified either after different types of exercise or in the secretome from control and insulin‐resistant human skeletal myotubes. We will also summarize studies on the impact of several myokines on pancreatic β‐cell proliferation, survival and function.