Bacterial antigens, such as intestinal microflora, are known to play a role in the pathogenesis of human inflammatory bowel disease (IBD). Tylosin, a macrolide antimicrobial agent, has proven to be effective in cat and dog chronic colitis, but the reasons underlying this efficacy are still unclear. In the present study we evaluated the effects of tylosin on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat, in comparison with the antibacterial drug metronidazole and the corticosteroid budesonide. Colitis was induced by a single intrarectal administration of 10 mg TNBS under light ether anesthesia. Tylosin (20 mg/kg twice a day), metronidazole (160 mg/kg twice a day) and budesonide (500 microg/kg once a day) were given orally for up to 6 days to separate groups of rats. The animals were sacrificed after 6 days and colonic lesions evaluated (colon weight, macroscopic and histologic damage, myeloperoxidase activity). Tylosin and metronidazole significantly lowered macroscopic lesion score, reduced colon weight, the severity of histologic lesions and myeloperoxidase activity; budesonide did not significantly change the parameters of colonic inflammation. These data indicate a protective effect of tylosin against intestinal inflammation, suggesting a major role for bacteria, anaerobes in particular, in the development of TNBS-induced mucosal damage.