Neonatal necrotizing enterocolitis (NEC), which is a disorder with poor prognosis, is considered to be caused by the coincidence of intestinal ischemia-reperfusion and systemic inflammation due to the colonization of pathogenic bacteria. Interleukin-8 (IL-8), a proinflammatory cytokine, plays an important role in the pathophysiology of NEC. It has recently been reported that IL-1 activates the IL-8 gene by regulating the transcriptional nuclear factor-B (NF-B) signaling pathways in intestinal cells. The protective role of maternal milk in NEC pathogenesis has been reported in both human and animal studies. We show here that human breast milk dramatically suppresses the IL-1-induced activation of the IL-8 gene promoter by inhibiting the activation pathway of NF-B. Moreover, we also show that human breast milk induces the production of IB-. These results suggest that human breast milk could be protective and therapeutic in neonates suffering from NEC by inhibiting the activation pathway of NF-B.