When discussing the scale of the occurrence of diseases of the digestive system in farm animals, particularly pigs in the weaning period, it may be beneficial to study physiological and nutritional factors that could potentially affect the growth, development, and modelling of the structure and function of the digestive tract. Taking into account the reports on the beneficial effects of ß-hydroxy-ß-methylbutyrate (HMB) administration in the prenatal period on the development of various systems it was assumed that the HMB supplementation to pregnant sows can influence intestinal development in the offspring during weaning. Thus, the present experiment was conducted to evaluate the effect of HMB treatment of pregnant sows on jejunum development in offspring at weaning. From 70th day until the 90th day of gestation, sows received either a basal diet (n = 12) or the same diet supplemented with HMB (n = 12) at the dose of 0.2 g/kg of body weight/day. HMB given during prenatal time reduced the thickness of the longitudinal muscle; the apoptotic cell index in epithelium also significantly decreased after the HMB supplementation. Vasoactive intestinal (poly)peptide (VIP) expression in submucosal ganglia significantly increases in prenatally HMB treated piglets. The same strong reaction was observed with the expression of occludin, claudin-3, E-cadherin, and leptin in the jejunal epithelium. The obtained results indicate that the administration of HMB to pregnant sows significantly influenced the expression of VIP, leptin and some proteins of the intestinal barrier of their offspring less influencing the basal morphology.