BACKGROUND: In acute illnesses, plasma glucose levels are often increased and generally parallel the severity of stress. Hyperglycemia caused by reduced insulin sensitivity and reduced insulin secretion is associated with increased susceptibility to infections. Maintaining blood glucose levels at or below 110 mg/dl reduces morbidity and mortality in critically ill patients. AIM: To measure the glucose and insulin responses of four commercially available enteral formulas compared with a standard meal reference product. MATERIAL AND METHODS: The glycemic index (GI) and the insulin index (II) were determined in a randomized, cross over protocol in 38 healthy volunteers between 18 and 46 years of age. Each subject underwent five tests: three with the standard meal (bread) and two with the study products. The enteral formulas were Clinutren HPR (whole protein of high protein value), Crucial (casein peptide based formula), Peptamen, (whey peptide based formula), Glytrol (formula for diabetics with whole protein with fiber). Each study product was evaluated 10 times. RESULTS: The diabetic formula and the high protein energy dense formulas induced a significantly lower GI (p <0.02) compared with the standard meal. The GI response did not appear to be due to enhanced insulin secretion. The other tested formulas had lower GI than the standard meal, but in addition they exhibited increased II The whey based peptide formulation produced the highest insulin response (p <0.03). CONCLUSIONS: Both GI and II are related to the concentration, form and type of protein contained in the enteral formula. The whey peptide formulation produced a low GI with the highest insulin index. Based on the low GI of these enteral products, all can be useful to provide nutritional support during metabolic stress, without adding an additional challenge to blood glucose management.