OBJECTIVE: Irisin, an exercise-induced myokine, is expressed and secreted by adipose tissue and skeletal muscle in association with obesity and insulin resistance. Obesity is a risk factor for type 2 diabetes (T2DM) and coronary artery disease (CAD). We aimed to investigate the association between serum irisin concentration and CAD in patients with T2DM. Subjects and Methods: Serum irisin levels were analyzed in 68 patients with T2DM and CAD (D-CAD), 64 patients with T2DM without CAD (D-WCAD) and 72 healthy control subjects. Serum adiponectin, Homeostasis model assessment of insulin resistance (HOMA-IR) and high sensitive C-reactive protein were analyzed. Results: Irisin levels were significantly lower in patients with T2DM than in control subjects, and was more decreased in D-CAD than in D-WCAD patients. Furthermore, Irisin correlated negatively with HOMA-IR, insulin, fasting plasma glucose and body mass index in all diabetic patients. Moreover, there was an association between irisin concentrations and CAD in T2DM patients in multivariate logistic regression analysis. Conclusions: Low serum irisin concentration associates with CAD in patients with T2DM.