The study was carried out to evaluate the beneficial effects of supplemental zinc (Zn) on the intestinal mucosal barrier function in Salmonella enterica serovar Typhimurium-challenged broiler chickens in a 42-day experiment. A total of 336 1-day-old male Arbor Acres broiler chicks were assigned to eight treatment groups. A 4×2 factorial arrangement of treatments was used in a completely randomized experimental design to study the effects of levels of supplemental Zn (0, 40, 80 and 120 mg/kg diet), pathogen challenge (with or without S. Typhimurium challenge), and their interactions. S. Typhimurium infection caused reduction of growth performance (P<0.05) and intestinal injury, as determined by reduced (P<0.05) villus height/crypt depth ratio and sucrase activity in the ileum, increased (P<0.05) plasma endotoxin levels, and reduced (P<0.05) claudin-1, occludin and mucin-2 mRNA expression in the ileum at day 21. Zn pre-treatment tended to improve body weight gain (P=0.072) in the starter period, to increase the activity of ileal sucrase (P=0.077), to reduce plasma endotoxin levels (P=0.080), and to significantly increase (P<0.05) the villus height/crypt depth ratio and mRNA levels of occludin and claudin-1 in the ileum at day 21. The results indicated that dietary Zn supplementation appeared to alleviate the loss of intestinal mucosal barrier function induced by S. Typhimurium challenge and the partial mechanism might be related to the increased expression of occludin and claudin-1 in broiler chickens.