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Abstract Background Adipokines are involved in the pathogenesis of metabolic disorders including obesity and type 2 diabetes mellitus (T2DM). This study investigates the levels of leptin, resistin, visfatin, secreted frizzled-related protein 5 (SFRP5), monocyte chemoattractant protein-1 (MCP-1) and retinol-binding protein 4 (RBP4) and their correlations with clinical parameters of overweight and T2DM. Methods We recruited overweight 50 patients with T2DM, 88 non-overweight patients with T2DM, 29 overweight and 100 non-overweight individuals devoid of T2DM for this study. The levels of studied adipokines were measured by enzyme-linked immunosorbent assay and correlated with clinical parameters. Results The levels of MCP-1 and SFRP5 were decreased while visfatin and RBP4 levels were increased in patients with T2DM compared to those in the control individuals (P < 0.01). Among patients with T2DM, leptin and resistin levels were higher while RBP4 levels were lower in patients with overweight T2DM compared to those in patients with non-overweight T2DM (P < 0.0001, 0.019 and 0.05, respectively). Leptin and MCP-1 levels were correlated with HOMA-IR, QUICKI and HOMA-β. Leptin/MCP-1 ratio was correlated with insulin levels, HOMA-IR and HOMA-β indexes. Resistin/RBP4, visfatin/MCP-1 and MCP-1/RBP4 ratios were strongly correlated with the levels of fasting glucose, HbA1c and HOMA-β. In addition, ROC curve analyses indicated a diagnostic potential of resistin/RBP4 and MCP-1/RBP4 indexes for T2DM (AUC = 0.81 and 0.83, respectively) and β-cell function (AUC = 0.76 and 0.74, respectively). Conclusions Adipokines (leptin, resistin, visfatin, SFRP5, MCP-1, and RBP4) are associated with overweight and T2DM and may serve as a potential prognostic marker and therapeutic intervention for overweight-related T2DM.