Macrophage migration inhibitory factor (MIF) is a cytokine that has potent anti-steroid effects and might be implicated in the pathogenesis of Ulecrative colitis (UC). We defined the functional role of MIF in the glucocorticoid (GC)-resistant inflammatory response in UC. Twenty-four colonic samples were obtained from GC responsive cases, GC refractory cases, Crohn's disease and controls. LPMC were isolated from surgical specimens. MIF was strongly expressed at mRNA levels in refractory cases rather than responsive cases with UC and controls. IL-8 production from LPMC was significantly reduced by GC addition in responsive cases but not in refractory cases. In refractory cases, anti-MIF Ab ameliorated GC-resistant IL-8 production and p38-MAPK activity of LPMC. In addition, p38-MAPK antagonist SB230580 also ameliorated GC-resistant IL-8 production. These results suggest that MIF has an additional proinflammatory activity through the p38-MAPK pathway in GC-resistant UC.