Background: Adiponectin, an adipocyte-derived hormone, is implicated in diabetes mellitus type 2 and atherosclerosis. The study was designed to investigate whether serum adiponectin levels in patients with both coronary artery disease (CAD) and diabetes mellitus type 2 (T2DM) are lower than in patients with CAD alone and control subjects.Objectives: In this present study, we measured serum adiponectin levels in consecutive CAD patients with and without T2DM and investigated whether decreased adiponectin is associated with risk factors of CAD.Materials and Methods: The study included 198 subjects, 138 patients with CAD (72 of whom had both CAD and T2DM), and 60 control subjects. We measured serum adiponectin, interleukin-6 (IL-6) and insulin by ELISA. In addition, Lipid profile, glucose and anthropometrical measurements were performed in all subjects.Results: The results revealed significant difference in serum adiponectin levels between patients with CAD+T2DM and patients with CAD alone (3.80±1.52 vs.5.25±2.35, P=0.007), between patients with CAD and control (5.25±2.35 vs.7.04±3.32, P=0.001), and between patients with CAD+T2DM and control (3.80±1.52 vs.7.04±3.32, P<0.001). Serum adiponectin level was significantly higher in women in contrast to men (5.97 ± 3.15 vs.4.62±2.81 mg/ml, P=0.002). Serum adiponectin levels were correlated significantly with insulin (r=-0.178, P=0.013), total cholesterol (r=-0.313, P<0.001), low density lipoprotein (r=-0.154, P=0.016), body mass index (r=-0.171, P=0.016), glucose (r=-0.202, P=0.006), HOMA-IR (r=-0.251, P=0.001), and IL-6 levels (r=-0.321, P=0.001). Adiponectin was correlated positively only with high density lipoprotein (r=0.389, P<0.001).Conclusions: It is speculated that increased insulin resistance and increase in other adipokines such as IL-6 may contribute to the decreased serum levels of adiponectin in patients with both CAD and T2DM.