Recently, a new approach has been proposed to estimate insulin sensitivity (S(I)) from an oral glucose tolerance test or a meal using an "integral equation". Here, we improve on the "integral equation" by resorting to a "differential equation" approach. The classic glucose kinetics minimal model was used with the addition of a parametric model for the rate of appearance into plasma of oral glucose (Ra). Three behavioral models of Ra were proposed: piecewise-linear (P), spline (S) and dynamic (D). All three models performed satisfactorily allowing a precise estimation of S(I) and a plausible reconstruction of Ra. Mean S(I) estimates were virtually identical: S(I)P = 6.81 +/- 0.87 (SE); S(I)S = 6.53 +/- 0.80; and S(I)D = 6.62 +/- 0.79. S(I) strongly correlated with the integral-equation index (I) S(I)I: r = 0.99, p < 0.01 for models D and S, and r 0.97, p < 0.01 for P. Also, SI compared well with insulin sensitivity estimated from intravenous glucose tolerance test in the same subjects (r = 0.75, p < 0.01; r = 0.71, p < 0.01; r = 0.73, p < 0.01, respectively, for P, S, and D models versus s(I)IVGTT). Finally, the novel approach allows estimation of SI from a shorter test (120 min): model P yielded S(I)R = 7.16 +/- 1.0 (R for reduced) which correlated very well with S(I)P and S(I)I (respectively, r = 0.94, p < 0.01; r = 0.95, p < 0.01) and still satisfactorily with S(I)IVGTT (r = 0.77, p < 0.01).