Bacteria have developed mechanisms to sequester host iron via chelators such as deferoxamine (DFO). Interestingly, DFO has been shown to stimulate intestinal epithelial cell inflammatory cytokine production in the absence of bacteria; however, this mechanism has not been elucidated. Intestinal epithelial cell production of IL- 6 and TNF- is elevated in various gastrointestinal pathologies, including necrotizing enterocolitis. Similarly, vascular endothelial growth factor and hepatocyte growth factor are essential to intestinal epithelial cell integrity. Therapeutic strategies that decrease IL-6 and TNF- while increasing VEGF and HGF therefore have theoretical appeal. We hypothesized that: 1) fetal human intestinal epithelial cells produce increased IL-6, TNF-, VEGF, and HGF during iron chelation; and, 2) the MAPK pathway mediates these effects. Fetal human intestinal epithelial cells were incubated and subsequently stimulated by iron chelation (0.1 mM DFO), with and without p38 MAPK, ERK, or JNK inhibition. Supernatants were harvested and IL-6, TNF-, VEGF, and HGF levels were quantified by ELISA. Activation of the MAPK pathways was confirmed by Western blot. DFO stimulation resulted in a significant increase in epithelial cell IL-6 and VEGF production, while yielding a decrease in HGF production (p<0.05). Unexpectedly, TNF -was not detectable. p38 MAPK, ERK, and JNK inhibition significantly decreased IL-6, VEGF, and HGF production (p<0.05). DFO increases fetal human intestinal epithelial cell IL-6 and VEGF expression, while causing an unexpected decrease in HGF expression, and no detectable TNF- production. Furthermore, chelator induced intestinal cell IL-6, VEGF, and HGF expression depends on the p38, ERK, and JNK MAPK pathways.