Background/Aims: The purpose of this study was to investigate the potential therapeutic roles of honey, prednisolone and disulfiram in an experimental model of inflammatory bowel disease. Another aspect of the study was to find out whether these substances have any effect on nitric oxide (NO) and free radical production. Methods: After the induction of colitis with trinitrobenzene sulfonic acid in 64 male rats, physiological saline, honey, prednisolone and disulfiram enemas were applied to the rats once daily for 3 days (acute treatment groups) or 7 days (chronic treatment groups). Control groups received only saline enemas. Rats were killed on the 4th or 8th days and their colonic mucosal damage was quantitated using a scoring system. Acute and chronic inflammatory responses were determined by a mucosal injury score, histological examination and measurement of the myeloperoxidase (MPO) activity of tissues. The content of malonylaldehyde (MDA) and NO metabolites in colon homogenates was also measured to assess the effects of these substances on NO and free oxygen radical production. Results: Estimation of colonic damage by mucosal injury scoring was found to be strongly correlated with the histologic evaluation of colon specimens. On the other hand, mucosal injury scores were not correlated with MPO, MDA or NO values. There were significant differences between the MPO results of chronic-control and chronic-honey groups, as well as chronic-control and chronic-prednisolone groups (p = 0.03 and p = 0.0007). The acute honey, prednisolone, and disulfiram groups had significantly lower MDA results compared to the acute control group (p = 0.04, p = 0.02, and p = 0.04). In terms of NO, there was no significant difference between the treatment and control groups. NO was found to have a strong relationship with MDA (p = 0.03) and MPO values (p = 0.001). On the other hand, MPO results were not found to be correlated with MDA values (p > 0.05). Conclusions: MPO activity is not directly proportional to the severity of the inflammation, but it may only determine the amount of neutrophil in the tissues. Inflammatory cells are not the sole intensifying factor in colitis. Therefore, mucosal injury scores may not correlate well with MPO activities. In an inflammatory state NO and MPO levels have a strong relationship, since NO is released from the neutrophils. In an inflammatory model of colitis, intrarectal honey administration is as effective as prednisolone treatment. Honey may have some features in the treatment of colitis, but this issue requires further investigation. Honey, prednisolone and even disulfiram also have some value in preventing the formation of free radicals released from the inflamed tissues. Prednisolone may also have some possible benefits in the inhibition of NO production in colitis therapy.