In neonates the vacuolated foetal-type enterocytes (VFE) play a key role in the transport of intact colostral and milk proteins from the lumen of the small intestine into the circulation and/or in the intracellular digestion of intestinal nutrients. The absorption of intact colostral macromolecules (including immunoglobulins, hormones and bioactive peptides) is important in the development of the immune and digestive systems of newborn piglets. The digestion of the intestinal content inside the VFE supports the luminal digestion of nutrients. The presence of apical canalicular system, which produces both the transport and the digestive vacuoles, is a key feature of VFE. The VFEs are gradually replaced by adult-type enterocytes. VFEs disappear gradually from the proximal part of the small intestine to the ileum. VFEs containing large (also referred to as giant) transport vacuoles disappear within the first 2–3 days after birth. VFEs containing digestive vacuoles are present for up to week 3 of life. In contrast, VFEs of intrauterine growth retarded piglets show abnormalities in their development of the apical area. The loss of VFEs is a good marker of the small intestine epithelium maturation.