<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objectives:</jats:title><jats:p>Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic peptide glucagon‐like peptide 2 (GLP‐2), which reduces TPN‐associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Term pigs obtained by cesarean delivery received from birth TPN alone (TPN; n = 7) or TPN with GLP‐2 (25 nmol · kg<jats:sup>−1</jats:sup> · d<jats:sup>−1</jats:sup>; GLP‐2; n = 8) or were fed sow milk enterally (n = 7). The small intestine was removed on postnatal day 6 to measure morphological responses and absorption of glucose, leucine, lysine and proline by intact tissues and brush border membrane vesicles and to quantify the abundances of mRNA and protein for enterocyte glucose transporters (SGLT‐1 and GLUT2).</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Relative to TPN alone, administration of GLP‐2 resulted in small intestines that were larger (<jats:italic>P</jats:italic> < 0.01), had greater abundances of mRNA and protein for SGLT‐1, but not for GLUT2, and had higher capacities to absorb nutrients (<jats:italic>P</jats:italic> < 0.01). Moreover, the intestines of GLP‐2 pigs were comparable in size and absorptive capacities with those of pigs fed sow milk enterally.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>Providing GLP‐2 to neonates receiving TPN prevents small intestine atrophy, results in small intestine absorptive capacities that are comparable to when nutrients are provided enterally and may accelerate the transition from TPN to enteral nutrition.</jats:p></jats:sec>