BACKGROUND: Inflammatory bowel diseases (IBD) affect both enteric neurons and enteric glia, with tumor necrosis factor-alpha (TNF-alpha) playing a role as an inflammatory mediator. AIMS: Analyze the effects of the anti-TNF monoclonal antibody on the myenteric plexus in an experimental model of colitis. METHODS: C57BL/6 mice received 3% dextran sodium sulfate (DSS) in drinking water for 7 days in both the DSS and DSS + ADA groups. The Sham group received water. The DSS + ADA group received ADA anti-TNF-alpha on day 2 of DSS intake. The ADA group was given water throughout the period and received an anti-TNF-alpha injection on day 2. The study evaluated the number of neurons per ganglion, and the area of the neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), pan-neuronal marker (PGP9.5), and tumor necrosis factor receptor 2 (TNFR2) immunoreactive (-ir). Double labeling of PGP9.5 with an enteric glial marker (GFAP) was also performed. RESULTS: DSS successfully induced experimental colitis (EC). TNFR2 was detected in the myenteric neurons in all groups. EC affected the enteric neurons, showing a decrease in the number of TNFR2-ir, ChAT-ir, nNOS-ir, and PGP9.5-ir neurons, whereas enteric glial cells increased in both the DSS and DSS + ADA groups. The DSS + ADA group showed number of nNOS-ir, ChAT-ir, and PGP9.5-ir neurons per ganglion similar to Sham group. EC also affected the neuronal profile, resulting in smaller areas in the DSS and DSS + ADA groups. CONCLUSION: Myenteric neurons are immunoreactive to the TNFR2. DSS altered the myenteric plexus, and anti-TNF monoclonal antibody treatment proved effective against EC due to preventing the pathology from developing.