The purpose of the present study was to test the efficacy of the empiric index SPIR (Second-phase Insulin Release) in the quantification of second-phase insulin secretion in the Zucker Fatty Rat. SPIR index is defined as the area under the curve of insulin between 8 and 90 min after an Intravenous Glucose Tolerance Test (IVGTT). The validation of such index was performed against the second-phase β-cell responsiveness index (Φ2) provided by C-peptide minimal model. To this aim, Φ2 and SPIR were simultaneously computed from IVGTT data, measured in six Zucker fatty rats (ZFR), 7-to-9week-old, and seven age-matched Zucker lean rats (ZLR). SPIR index showed a significant linear correlation with Φ2 (Pearson's correlation coefficient, r = 0.91, R-square = 0.82, P<;0.001). Moreover, both Φ2 (P<;0.001) and SPIR (P<;0.001) showed a significant increase, in the ZFRs, compared to control group (ZLR). These findings suggest that the SPIR index is able to provide similar information of Φ2, in the evaluation of the second-phase insulin secretion and of its alteration in Zucker Fatty Rats. Thus, the study proposes the SPIR, as a suitable index for a simple, reliable and low-cost quantification of the second-phase insulin secretion in ZFR.