The innate immune system and its major mediators, i.e., cytokines, are increasingly recognized as being of crucial importance in metabolic inflammation as observed in morbid obesity and type 2 diabetes (T2D). Morbid obesity is commonly associated with adipose tissue inflammation. Adipose tissue inflammation is characterized by an increased expression of various pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 and -6, and by a rather heterogenous cellular infiltrate including monocytes/macrophages, neutrophils, B lymphocytes, T lymphocytes, and others. It has been demonstrated that in patients with severe obesity and fatty liver disease, expression of these pro-inflammatory cytokines in adipose tissue is 100–1000 times higher compared with that in the liver. Therefore, the adipose tissue can be considered in the state of severe obesity as the “cytokine factory” of the body. Rapid weight loss almost entirely eliminates pro-inflammatory cytokines in the adipose tissue, and therefore provides a very potent anti-inflammatory strategy. In conclusion, there is increasing evidence that peripheral tissues such as the adipose tissue may affect disease processes in target organs such as the liver, pancreas, heart, or blood vessels, and may therefore significantly contribute to chronic inflammation as observed in obesity and T2D.