Increasing evidence shows that obesity is the critical factor in shaping cardio-metabolic phenotypes. However, the pathogenic mechanisms remain incompletely clarified. According to the published reports, adipose tissue communicates with several diverse organs, such as heart, lungs, and kidneys through the secretion of various cytokines named adipokines. The adipocytes isolated from obese mice or humans are dysfunctional with aberrant production of pro-inflammatory adipokines, which subsequently induce both acute and chronic inflammatory reaction and facilitate the process of cardio-metabolic disorder complications. Furthermore, the microenvironment within adipose tissue under obese status also influence the secretion of adipokines. Recently, given that several important adipokines have been completely researched and causally involved in various diseases, we could make a conclusion that adipokines play an essential role in modulating the development of cardio-metabolic disorder diseases, whereas several novel adipokines continue to be explored and elucidated. In the present review, we summarized the current knowledge of the microenvironment of adipose tissue and the published mechanisms whereby adipocytes affects obesity and cardiovascular diseases. On the other hand, we also provide the evidence to elucidate the functions of adipokines in controlling and regulating the inflammatory reactions which contribute to obesity and cardiovascular disease.