Background: The fluctuation in serum caveolin-1 (Cav-1) concentrations is an important indicator of many diseases. Irrespective of the actual cause, a significant reduction of serum Cav-1 is associated with a significant increase in insulin secretion and hyperinsulinemia. The aim of the current study was to evaluate the relationship between serum Cav-1, serum vaspin and visfatin in newly diagnosed men with T2DM. Methods: Eighty-two newly diagnosed men with T2DM were matched for age and body mass indexes (BMIs) with a similar number of non-diabetic men. Serum Cav-1, vaspin and visfatin were assessed through enzyme-linked immunosorbent assay. Fasting serum glucose (FSG), glycohaemoglobin A1C (HbA1c) were both measured using automated method. In addition, waist-circumferences, waist-hip ratio, systolic (SBP), and diastolic blood pressure (DBP) were also obtained. Results: Serum concentration of Cav-1(ng/mL) was significantly low in men newly diagnosed with T2DM, (2. 334±, 0. 7627) compared with non-diabetic controls (4. 321±, 1. 143), p< 0. 0001. In contrast, patients with T2DM exhibited significantly higher serum concentrations of vaspin and visfatin (ng/mL), 142. 4±, 60. 53) and 2. 99±, 1. 091), than controls, 81. 53±, 39. 32) and 1. 456±, 0. 654), respectively, p< 0. 0001. Expectedly, patients with T2DM have significantly higher FSG, HbA1c, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Conclusions: There was an inverse significant relationship between Cav-1 and vaspin, visfatin, HbA1c, FSG, and hypertension. This study suggests that serum Cav-1 can be used as a diagnostic marker to predict T2DM in individuals and families under high risk.