Background/Aims: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) in children with Crohn`s disease (CD) during infliximab therapy. Methods: We enrolled 20 CD patients who received infliximab treatment for 1 year. Periph￢eral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals. Re￢sults: A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25+ FOXP3+ was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008). Conclusions: Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful thera￢peutic tool, where restoration of TIM-3, HBD-2 and the func￢tion of Tregs may repair the dysfunctional immunoregulation in CD. (Gut Liver 2015;9:370-380)