Objective: The purpose of this study was to quantify the effects of glycemic index on postprandial glucose excursion (PPGE) in children with type 1 diabetes receiving multiple daily injections and to determine optimal insulin therapy for a low-glycemic index meal. Research and design methods: Twenty subjects consumed test breakfasts with equal macronutrient contents on 4 consecutive days; high-and low-glycemic index meals (glycemic index 84 vs. 48) were consumed with preprandial ultra-short-acting insulin, and the low-glycemic index meal was also consumed with preprandial regular insulin and postprandial ultra-short-acting insulin. Each child's insulin dose was standardized. Continuous glucose monitoring was used. Results: The PPGE was significantly lower for the low-glycemic index meal compared with the high-glycemic index meal at 30-180 min (P<0.02) when preprandial ultra-short-acting insulin was administered. The maximum difference occurred at 60 min (4.2 mmol/l,P<0.0001). Regular insulin produced a 1.1 mmol/l higher PPGE at 30 min compared with ultra-short-acting insulin (P = 0.015) when the low-glycemic index meal was consumed. Postprandial ultra-short-acting insulin produced a higher PPGE at 30 and 60 min compared with preprandial administration when the low-glycemic index meal was consumed. The maximum difference was 2.5 mmol/l at 60 min (P<0.0001). Conclusions: Low-glycemic index meals produce a lower PPGE than high-glycemic index meals. Preprandial ultra-short-acting insulin is the optimal therapy for a low-glycemic index meal.