Adipose tissue is one of the main sources of inflammatory mediators, with interleukin-6 (IL-6) among them. Although high systemic levels of inflammatory mediators are cachectogenic and/or anorexic, today it is a widely propagated thesis that in the background of obesity, a low level of chronic inflammation can be found, with IL-6 being one of the many suggested mediators. This paper reviews the studies describing elevated IL-6 levels in obese patients and the role of adipocytes and adipose-tissue macrophages in the production of IL-6. The secretion of IL-6 is regulated by several physiologic or pathologic factors: hormones, cytokines, diet, physical activity, stress, hypoxia, and others. Adipose tissue-derived IL-6 may have an effect on metabolism through several mechanisms, including adipose tissue-specific gene expression, triglyceride release, lipoprotein lipase downregulation, insulin sensitivity, and so on. Having a better understanding of these mechanisms may contribute to the prevention and treatment of obesity.