Background: The Food Insulin Index (FII) is a novel classification of single foods based on insulin responses in healthy subjects relative to an isoenergetic reference food. Objective: Our aim was to compare day-long responses to 2 nutrientmatched diets predicted to have either high or low insulin demand in healthy controls and individuals with type 2 diabetes (T2DM). Design: Twenty adults (10 healthy adults and 10 adults with T2DM) were recruited. On separate mornings, subjects consumed either a high- or low-FII diet in random order. Diets consisted of 3 consecutive meals (breakfast, morning tea, and lunch), matched for macronutrients, fiber, and glycemic index (GI), but with 2-fold difference in insulin demand as predicted by the FII of the component foods. Postprandial glycemia and insulinemia were measured in capillary plasma at regular intervals over 8 h. Results: As predicted by their GI, there were no differences in glycemic responses between the 2 diets in either group (mean ± SEM; healthy: 6.2 ± 0.2 compared with 6.1 ± 0.1 mmol/L $ min, P = 0.429; T2DM: 9.96 1.3 compared with 10.3 ± 1.6 mmol/L · min, P = 0.485). Compared with the high-FII diet, mean postprandial insulin response over 8 h was 53% lower with the low-FII diet in healthy subjects (mean ± SEM; incremental AUCinsulin 31,900 ± 4100 pmol/L ·min compared with 68,100 ± 11,400 pmol/L · min, P = 0.003) and 41% lower in subjects with T2DM (mean ± SEM; incremental AUCinsulin 11,000 ± 1800 pmol/L · min compared with 18,700 ± 3100 pmol/L · min, P = 0.018). Incremental AUCinsulin was statistically significantly different between diets when groups were combined (P = 0.001). Conclusions: The FII algorithm may be a useful tool for reducing postprandial hyperinsulinemia in T2DM, thereby potentially improving insulin resistance and b-cell function. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000654954.