This study underlines the beneficial use of excess dietary zinc in preventing colitis and inflammatory events. Zn-induced gene expression profiles were analyzed at ileum and colon level. A total number of 101 profiles were found differentially expressed during Zn supplemented diet, with an unbalanced pattern between these two tissues. A largest number of genes were found up-regulated in colon (22 genes), unlike the ileum (6 genes). At the other side, the number of down-regulated genes was higher in ileum (63 genes) against the colon (15 genes). Very few common profiles were detected in these two tissues, 3 up- and 2 down-regulated genes respectively. Genes coding for metallothioneins (Mt1, Mt2) and for phosphatidylinositol-4-phosphate 5-kinase (Pip5k1a) were found commonly up-regulated in ileum and colon, with the highest FC values. Genes coding for the zinc transporter of solute carrier family 39 (Slc39a4) and for lymphotoxin B (Ltb) were found commonly down-regulated with among the lowest FC values. Despite the different patterns, functional clustering of expressed genes converged for substantially the same physiological activities in both ileum and colon: intestinal tissue protection and epithelium reestablishment, immune system regulation as well as digestive and metabolic targeted functions. Overall design: Three groups of mice were randomized to receive distinct doses of ZnCl2 solutions administered in the drinking water while a control group consisted in standard uncontaminated drinking water. After 15 days of Zn treatment, mice are sacrificed and sections from the median colon and terminal ileum were collected and processed for transcriptomic analyses.