Nutritional support of preterm infants by total parenteral nutrition (TPN) is common; however, TPN compromises intestinal structure and enzyme activity. Our goal was to develop a piglet model to assess the effect of limited enteral stimulation with formula and insulin-like growth factor-I (IGF-I) on intestinal morphology and enzyme activity. A nutritionally complete TPN solution was infused for 7 days and piglets were gavaged twice daily with 4 ml sterile water, formula, or formula containing 1,000 µg/l IGF-I. Litter mate piglets fed formula served as orally fed controls. On day 7, body weights and plasma hormone profiles of TPN and orally fed piglets were similar. However, intestinal weight, jejunal and ileal villus height and surface area, and mucosal lactase and sucrase activity of TPN piglets was reduced by ∼50%. No effect of limited enteral stimulation or IGF-I was observed likely due to the small volume of formula administered enterally, which resulted in a low dose of IGF-I (4.3 µg IGF-I/kg/day).