Obesity is defined as excessive accumulation of body fat in proportion to body size. When obesity occurs, the functions of adipose tissue may be deregulated, which is termed as adiposopathy. Adiposopathy is an independent risk factor for many diseases, including diabetes and cardiovascular diseases. In overweight or obese subjects with adiposopathy, hyperlipidemia exerts lipotoxicity in pancreatic islet and liver and induces pancreatic β cell dysfunction and liver insulin resistance, which are the decisive factors causing type 2 diabetes. Moreover, adipokines have been shown to play important roles in the regulation of glucose homeostasis. When adiposopathy occurs, abnormal changes in the serum adipokine profile correlate with the development and progression of pancreatic β cell dysfunction and insulin resistance in peripheral tissue. The current paper briefly discusses the latest findings regarding the effects of adiposopathy-related lipotoxicity and cytokine toxicity on the development of type 2 diabetes.