Enterochromaffin (EC) cells in the gastrointestinal (GI) mucosa are the main source of serotonin (5-hydroxytryptamine (5-HT)) in the body. 5-HT is implicated in the pathophysiology of many GI disorders including functional and inflammatory bowel disorders. Herein we studied the role of interleukin 13 (IL-13) in EC cell biology by utilizing IL-13-deficient (IL-13-/-) mice and BON cells (a model for human EC cells). The numbers of EC cells and 5-HT amount were significantly lower in enteric parasite, Trichuris muris-infected IL-13-/- mice compared with the wild-type mice. This was accompanied with increased parasite burden in IL-13-/- mice. Treatment of naive and infected IL-13-/- mice with IL-13 increased EC cell numbers and 5-HT amount. BON cells expressed IL-13 receptor and in response to IL-13 produced more 5-HT. These results provide novel information on IL-13-mediated immunological control of 5-HT in the gut, which may ultimately lead to improved therapeutic opportunities in various GI disorders.