IL‐6 is a pleiotropic cytokine that participates in normal functions of the immune system, haematopoiesis, metabolism, as well as in the pathogenesis of metabolic and cardiovascular diseases. Both pro‐ and anti‐inflammatory roles of IL‐6 have been described, which are distinguished by different cascades of signalling transduction, namely classic and trans‐signalling. The present review summarizes the basic principles of IL‐6 signalling and discusses its roles in diabetes and associated cardiovascular complications, with emphasis on the different outcomes mediated by the two modes of IL‐6 signalling and the value of developing therapeutic strategies to specifically target the deleterious trans‐signalling of IL‐6.