Skeletal muscles play an active role in regulating the metabolic homeostasis through their ability for relating to adipose tissue and endocrine hormones. Contraction of the skeletal muscle leads to increased release of several myokines, such as irisin, which is able to interact with the adipose tissue. Physical activity promotes the irisin mechanism by augmenting the peroxisomes (PGC1-α ) in the skeletal muscle. Afterwards, an elevation occurs in the membrane protein of fibronectin type III domain-containing protein 5 (FNDC5) in muscle, ultimately resulting in production of irisin. The expression of irisin and FNDC5 converts white adipose into the brown type and increases energy consumption by the whole body hindering obesity and diabetes. The effects of regular exercise training on preventing obesity, diabetes, and the related complications, as well as improving health have already been proven. However, the point is that these beneficial effects are due to the cellular-molecular mechanisms, which are still under discussion. In this review, we searched the online databases, including scientific information database (SID), Google Scholar, PubMed, Science Direct, and Scopus. The following keywords were used: training, physical activity, myokine, adipose tissue, PRDM16, PGC-1α , PPARγ , SIRT1, FGF21, bone morphogenetic protein, neurugolin, VEGF, and IL-15. All the articles, including research studies, review articles, descriptive and analytical studies, in addition to cross-sectional researches published during 1998-2017 were reviewed. According to the obtained results, it seems that expression of irisin and FNDC5 converts the white adipose into brown adipose resulting in increased energy consumption. It has been proven in the literature that regular exercise training prevents obesity, diabetes, and the related complications, as well as improving health.