Overweight or obesity has become a critical health problem in the world. The association of obesity with type 2 diabetes mellitus (T2D) has been recognized for decades, and the major basis for this link is the ability of obesity to engender insulin resistance (IR). Adipose tissue is not only an energy depot but also an active endocrine organ. Furthermore, fat distribution in the body is important for the progress of IR. Many studies show that visceral fat is more important in relation to IR than subcutaneous fat. Circulating free fatty acids (FFAs) derived from adipocytes are elevated in many IR states and have been suggested to be a main underlying mechanism of IR in obesity-associated T2D. However, compelling evidence demonstrates that adipocytokines including several adipocyte-derived cytokines or hormones are also involved in obesity-induced IR. Therefore, we hypothesise that adipocytokines may be a bridge connecting obesity and IR, and abnormal fat depot distribution or visceral fat/subcutaneous fat ratio (V/S ratio) in obesity also could be a primer for IR. When visceral fat accumulates and V/S ratio deteriorates , just like a primer,in visceral obesity it should begin to display unhealthy effect begin to take place in the body. In addition to it, as one of physiological regulation mechanisms of the body, most of the adipocytokines from the visceral fat reduce the visceral fat volume or normalize the V/S ratio. Actually, on the contrary, with serum a change in the serum adipocytokine level and an imbalance of them in the body for a long term, it will become a pathological condition and various kinds of effects may contribute to the development of IR. If confirmed, this hypothesis may lead to the formulation of new pathogenesis and new therapeutic approaches to IR. For example, an effective slimming pill will be assessed in future on the basis of the decrease of V/S and serum adipocytokines level rather than of body weight.