Neonates with intrauterine growth restriction (IUGR) are prone to suffer from digestive diseases. Using neonatal pigs with IUGR, we tested the hypothesis that IUGR may induce alterations in the developmental pattern of intestinal barrier and thereby may be responsible for IUGR-associated increased morbidity. Piglets with a birth weight near the mean birth weight (+/- 0.5 SD) were identified as normal birth weight (control) and piglets with a mean -2 SD lower birth weight (-30%) were defined as piglets with IUGR. The developmental pattern of intestinal structure, transcriptornic profile, and bacterial colonization was investigated from birth to d 5 postnatal. At birth, intestinal weight and length, ileal and colonic weight per unit of length, and villous sizes were lower (P < 0.05) in piglets with IUGR than in same-age control piglets. These IUGR-induced intestinal alterations further persisted, although they were less marked at d 5. Counts of adherent bacteria to ileal and colonic mucosa were greater (P < 0.05) in 2-d-old piglets with IUGR than in same-age control piglets. Dynamic analyses of the transcriptomic profile of the intestine revealed molecular evidence of IUGR-induced intestinal growth impairment that may result from a change in the cell proliferation-apoptosis balance during the first days of life, while a protective process would occur later on. In addition, changes in the expression of several genes suggest a pivotal role of both glucocorticoids and microbiota in driving IUGR intestinal development during the neonatal period. J. Nutr. 140: 925-931, 2010.