The first days of life are crucial for the development of intestinal mucosa in mammalian neonates. Its development consists of tissue growth and maturation, in particular of the epithelium. During postnatal development, the first 24 h are the most important, as this is when intensive remodeling of epithelial cells linked with cell replacement and functional modification occurs. An infant’s small intestine adapts to new digestive functions and feed. In this period, luminal and systemic hormones and growth factors play an important role. Sow colostrum and milk contain a high concentration of hormones and growth factors stimulating growth and maturation of small intestinal mucosa. Feeding animals milk formulas devoid of these bioactive factors slows down intestinal maturation in comparison with natural feeding by the mother. Recent studies demonstrate the great impact of nutritional, hormonal, paracrine and autocrine factors on epithelial cell proliferation and differentiation processes.