Leukotrienes are potent lipid mediators derived from the metabolism of arachidonic acid by the enzyme 5-lipoxygenase. Elevated levels of the pro-inflammatory leukotriene LTB4 have been found in preclinical models of IBD as well as in colon tissue from individuals with IBD. We therefore determined the extent to which absence of 5-lipoxygenase derived lipid mediators would alter the colitis in IL10-/- mice, a model of human IBD. IL10^-/-/5LO^-/- mice were generated and were healthy. Spontaneous colitis developed in both IL10^-/- and IL10^-/-/5LO^-/- mice. Absence of 5-lipoxygenase did not delay the onset or alter the severity of inflammation in NSAID treated IL10^-/- mice. At an early time point, 3 d after NSAID treatment was initiated, a qualitative increase in the number of dendritic cells and CD4⁺ T cells was noted in the colons of IL10^-/-/5LO^-/-; however this difference was no longer present after 14 days of NSAID treatment. Absence of 5-LO did not alter the degree of neutrophil infiltration into the in this model. Absence of 5-lipoxygenase do not alter the development of IFN producing Th1 type CD4⁺ T cells or IL-17 producing CD4⁺ T cells. Absence of 5-LO-derived mediators did not alter the expression of the adhesion molecules ICAM-1 and P-selectin. Development of colitis in IL10^-/- mice was associated with increased levels of the 5-LO-derived anti-inflammatory lipoxin LXA4. These studies demonstrate that 5LO-derived leukotrienes are not required for the development or maintenance of spontaneous or NSAID-induced colonic inflammation in IL10^-/- mice.