Inflammatory bowel disease (IBD) is an idiopathic disorder characterized by chronic abdominal pain and, on occasion, organ pathology. It is initiated by a traumatic insult inducing acute colitis, i.e., colon inflammation, and, over time, develops into a chronic condition due to failure of the inflammatory cascade to self-regulate correctly. The etiologies of inflammatory bowel disease are poorly understood and pain management therapies are limited, so this work attempted to gain a deeper understanding of methods that may potentially affect current practices in the treatment of IBD. A key feature of IBD is the large increase in immune cells, granulocytes, and pro-inflammatory cytokines, which results in an expansion of the submucosal area. This project was born out of a desire to better understand the neurogenic component of the inflammatory process in 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced colitis. TNBS, dissolved in ethanol, is delivered by intracolonic infusion and the epithelial mucosal barrier is compromised over time producing a diffuse inflammation in the distal colon characterized by ulceration, edema, leukocyte infiltration, and pro-inflammatory cytokine production. Because 6-diazo-5-oxo-l-norleucine (DON), a glutaminase (GLS) inhibitor, is known to reduce neurogenic inflammation in a somatic model of inflammation, we hypothesized that colonic administration of DON prior to induction of TNBS colitis will reduce inflammation in the rat colon. We specifically aimed at evaluating the anti-inflammatory effect of DON in a colon that has received TNBS, determining its protective properties by analyzing TNBS-induced leukocyte infiltration, maintenance of epithelial integrity, and preservation of nerve fiber interaction with the lamina propria. Lastly, we studied the ability of DON to attenuate the increase in pro-inflammatory mediator mRNA during TNBS-induced colitis. Based on our results we accept our hypothesis, as we saw a decrease in edema, pro-inflammatory cell infiltration, and epithelial damage in colons that had been pre-treated with DON.