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 is interleukin-8 (IL-8), a proinflammatory cytokine and potent neutrophil attractant that has been implicated in the initiation and perpetuation of IBD. Although bile acids are classically known for their role in lipid digestion they are also capable of activating nuclear and membrane receptors that regulate immune responses in the intestine and the liver. The aim of this study was to investigate the effects of the naturally-occurring bile acids, ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA), on IL-8 secretion from U937 monocytes. IL-8 release from U937 monocytes was induced with either bacterial lipopolysaccharide (LPS) [1 µg/mL] or the endogenous proinflammatory cytokine, TNFα [5 ng/mL] for 1hr. Cells were co-treated with either UDCA or DCA. Supernatants were then analysed for IL-8 protein by sandwich ELISA. IL-8 mRNA expression was assessed by qPCR. Cytotoxic effects of bile acids were determined by detection of lactate dehydrogenase release. Statistical analysis was performed using one way ANOVA with the Tukey-Kramer post test. LPS and TNFα induced a 6.4 ± 1.5 and 2.2 ± 0.3 fold increase in IL-8 release from U937 monocytes, respectively (n = 5; p < 0.05). UDCA, at concentrations of 200 µM and 500 µM, attenuated LPS-induced IL-8 release to 75 ± 7.9% and 34 ± 4.5% of controls, respectively (n = 5; p < 0.05). DCA, 100 and 150 µM, also exerted a concentration-dependent inhibition of LPS stimulated IL-8 release to 54 ± 12.3% and 44 ± 8.7% of controls (n = 5 p < 0.05). TNFα-stimulated IL-8 release was inhibited to 39 ± 4.6% of controls by UDCA (500 µM) and to 42 ± 5.5% by DCA (200 µM) (n = 4 p < 0.05). UDCA (500 µM) and DCA (150 µM) also reduced LPS-induced IL-8 mRNA expression to 24.6 ± 9.7% of control (n = 4; p < 0.05) and 11.4 ± 7.7% respectively. UDCA and DCA did not exert toxic actions at any of the concentrations tested. The taurine-conjugates of the bile acids, tauroursodeoxycholic acid (TUDCA) and taurodeoxycholic acid (TDCA) did not have any effect on LPS or TNFα-induced cytokine production. The results of this study demonstrate that the naturally-occurring bile acids, UDCA and DCA, attenuate IL-8 release from monocytes through inhibition of mRNA expression for the cytokine. Such actions suggest that UDCA and DCA may exert anti-inflammatory effects in vivo and that manipulation of the colonic bile acid pool could prove useful as a new therapeutic strategy for IBD.