Background: The Irisin is a myokine associated with the improvement on insulin resistance caused by diet and increased physical energy expenditure. Recent studies have shown that patients with Type 2 Diabetes Mellitus (T2DM) have reduced levels of irisin, showing it as a potential marker for various endocrine and cardiovascular diseases. This study aimed to verify if T2DM patients never treated or without ongoing treatment have reduced levels of irisin when compared to individuals with other metabolic profiles. Methods and Findings: Systematic review of the literature, considering the primary studies published in 2012 to 2016, with the outcome Irisin levels in patients never treated or without current treatment in the ambience of Type 2 Diabetes Mellitus. The search was conducted through the electronic database Scopus (Elsevier), using the key words: "Irisin", "Human" and "Diabetes Mellitus". From the 91 studies found, 8 met the eligibility criteria. Significant differences were found on levels of irisin in patients with T2DM compared to normoglycemic individuals, obese and/or pre-diabetic. On average, there was a reduction of 15 pg/ml in plasma levels of irisin in diabetics. However, a minority of studies says that this relationship does not exist. Conclusion: Irisin reduced levels were found in patients with T2DM and is also related to lipid profile, with the risk of developing endocrine diseases, such as diabetes and obesity, and high risk for cardiovascular diseases because of its relationship with endothelial dysfunction. This generates the need for research in order to explore the isolation and clinical use of irisin for treatment of disorders related to imbalance in energy demand, obesity and diabetes. Descriptors: Irisin, Human, Diabetes Mellitus.