Insulin plays a key role both in diabetes and in obesity, so a better understanding of insulin secretion in obesity could have important clinical and therapeutic implications. We analyzed the insulin secretion and glucose response through intravenous glucose tolerance test (IVGTT) in non diabetic obese subjects. Seventy obese subjects have been enrolled. All underwent anthropometrical evaluation and a 75 g oral glucose tolerance test. Based on glucose tolerance subjects were divided into 5 groups: normal glucose tolerance (Ob-NGT) (n=29), impaired fasting glucose (Ob-IFG) (n=2), impaired glucose tolerance (Ob-IGT) (n=18), Ob-IGT/IFG (n=6), Ob-T2D (n=6). Control group was lean subjects with NGT. Then, all underwent IVGTT and glucose, insulin and C-peptide concentrations were measured every 2 minutes in the first 10 minutes and then 20’, 30’, 40’, 50’, 60’. We evaluated acute insulin response (AIR) that corresponds at first 10 min after glucose infusion by mathematical model and the insulin sensitivity was by “calculated sensitivity index” (CSi), which is based on plasma insulin/glucose measurements carried out during 50 min. It shows a good degree of correlation with M of Clamp. β-cell function has been evaluated by Disposition Index (DI). The population was homogeneous for body mass index (BMI) and fat mass. Ob-T2D showed a loss of the first-phase insulin secretion (FPIS) when compared with Lean-NGT and Ob-NGT. Ob-IGT and Ob-IFG/IGT showed no reduction in the FPIS compared to Ob-NGT but an increase in the second phase of secretion when compared to both Ob-T2D and Ob-NGT. When compared with the control group Lean-NGT, the entire population of obese subjects showed an increase insulin secretion. Since insulin secretion is dependent on insulin sensitivity, we evaluated CSI and DI, calculated by IVGTT. We observed a significant difference between different obese groups and in the Lean-NGT group in CSì (p=0.000). Similarly, DI was significantly reduced in obese subjects compared with Lean-NGT and, in the obese groups, decreased with worsening of the degree of glucose tolerance (p=0.000). Although preliminary, our date showed the presence of several alterations in insulin sensitivity and/or secretion in obese subjects when compared with Lean-NGT subjects.