The objective of this study was to evaluate effects of dietary L-lysine on the intestinal mucosa and expression of cationic amino acid transporters (CAT) in weaned piglets. Twenty-eight piglets weaned at 21 days of age (Duroc × Landrace × Yorkshire; 6.51 ± 0.65 kg body weight) were assigned randomly into one of the four groups: Zein + LYS (zein-based diet + 1.35 % supplemental lysine), Zein - LYS (zein-based diet), NF (nitrogen-free diet), and CON (basal diet). The experiment lasted for 3 weeks, during which food intake and body weight were recorded. At the end of the trial, blood was collected from the jugular vein of all pigs, followed by their euthanasia. Dietary supplementation with lysine enhanced villus height and crypt depth in the jejunum (P < 0.05). Jejunal mRNA levels for the b(0,+)-AT, y(+)LAT1 and CAT1 genes were greater (P < 0.05) in the Zein + LYS group than in the control, and the opposite was observed for CAT1. Dietary content of lysine differentially affected intestinal CAT expression to modulate absorption of lysine and other basic amino acids. Thus, transport of these nutrients is a key regulatory step in utilization of dietary protein by growing pigs and lysine in the diet influences the expression of amino acid transporters in the small intestine.