Interleukin 6 (IL-6) is an inflammatory cytokine known to be elevated in chronic diseases and after insults such as trauma and infection. Although necessary for the development of B cells and Th17 cells, IL-6, at elevated levels, can also cause tissue damage and lead to a rise in inflammation. Previous work in our laboratory has shown that IL-6 is increased both systemically and in multiple organ systems including the ileum after ethanol exposure and burn injury. As this combined insult causes elevated intestinal morphological damage, tight junction protein localization alterations, and phosphorylated myosin light chain levels, we sought to determine the role of IL-6 in these intestinal responses using a model of binge ethanol exposure and burn injury. Interleukin 6 antibody treatment after the combined insult reduced morphological changes in the ileum, bacterial translocation, and phosphorylated myosin light chain levels relative to either injury alone. Zonula occludens protein 1 and occludin localization was also reestablished in wild-type mice given IL-6 antibody after ethanol and burn. Interleukin 6-knockout mice given ethanol and burn injury also had reduced intestinal damage; however, no changes in bacterial translocation or tight junction protein localization were observed as compared with similarly treated wild-type mice. These data suggest that IL-6 may have a role in intestinal tissue damage observed after the combined insult of binge ethanol exposure and burn injury, although complete loss of IL-6 does not seem to be beneficial in this model. Modulation of IL-6 may present a new option for preventing intestinal damage and associated inflammation after a combined insult of ethanol exposure and burn injury.