Inflammatory Bowel Disease (IBD)is a group of disorders characterised by chronic intestinal inflammation. The intestines of patients with IBD contain increased numbers of newly recruited monocytes, which augment the level of several inflammatory mediators in the gut. Among these inflammatory mediators are interleukin-8 (IL-8),a pro-inflammatory cytokine and potent neutrophil attractant that has been implicated in the initiation and perpetuation of IBD. Monocytes have also been shown to release huge amounts of TNFα, another pro-inflammatory cytokine which has been shown to have severe detrimental effects on the colonic epithelial barrier. Although bile acids are classically known for their roles in lipid digestion, they are also known to regulate immune responses in the intestine and to have roles to play in IBD pathogenesis. The aim of this study was to investigate the effects of the naturally-occurring bile acid, ursodeoxycholic acid (UDCA) on IL-8 secretion from U937 monocytes and also determine the role of monocytes in regulating colonic epithelial barrier function.IL-8 release from U937 monocytes was induced with either bacterial lipopolysaccharide (LPS) [1 µg/mL] or the endogenous pro-inflammatory cytokine, TNFα [5 ng/mL] for 24 hrs. Cells were co-treated with UDCA. Supernatants were then analysed for IL-8 protein by ELISA. IL-8 mRNA expression was assessed by qPCR. Cytotoxic effects of UDCA were determined by detection of lactate dehydrogenase release. Barrier function was assessed by measurement of TER. Statistical analysis was performed by one way ANOVA with the Tukey-Kramer post test.Treatment of U937 monocytes with TNFα- or LPS-induced 9.8 ± 1.2 and 7.9 ± 1.6 fold increases in IL-8 release, respectively (n = 5 – 7; p < 0.001). UDCA, at concentrations of 25, 50 and 100 µM, reduced TNFα-induced IL-8 release to 5.3 ± 0.8, 4.9 ± 0.6 and 3.5 ± 0.4 fold, respectively (n = 5; p < 0.001).UDCA also significantly attenuated basal IL-8 release (n=5; p < 0.001) and inhibited IL-8 mRNA expression. (n = 4; p < 0.05). In contrast, UDCA had no effect on LPS-driven IL-8 release. At the concentrations employed, UDCA did not exert toxic effects (n=3). Western blot analysis confirmed UDCA does not target the P38 MAP kinase pathway to attenuate IL-8 release (n=4). However, inhibition of NFkB, a known target of UDCA-induced signaling, resulted in attenuation of both TNFα- and LPS-driven cytokine release (n=4). Co-culture experiments revealed that monocytes added to the basolateral compartment of IFNy-primed T84 cell monolayers significantly reduced TER (n = 3, p < 0.05). However, treatment of monocytes with UDCA [100 µM] attenuated this effect (n = 3, p < 0.05). In conclusion, our data suggest that UDCA, by virtue of its anti-inflammatory effects on monocytes, may prove to be a useful therapeutic target for IBD.