Neutrophils have been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and anti-TNF- mAb (i.e., infliximab) therapy is demonstrated to be effective in the induction of clinical remission and mucosal healing in these patients. However, how anti-TNF- mAb regulates the functions of neutrophils is still unknown. Herein, we found that anti-TNF- therapy significantly downregulated infiltration of neutrophils in inflamed mucosa of IBD patients. Importantly, anti-TNF- mAb could inhibit neutrophils to produce proinflammatory mediators, such as ROS, calprotectin, IL-8, IL-6, and TNF-. These data indicate that TNF- plays a critical role in the induction of mucosal inflammatory response, and that blockade of TNF- modulates intestinal homeostasis through balancing immune responses of neutrophils.