Background/aim: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and methods: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days. Results: IP and IR pentoxifylline similarly and significantly reduced damage and histopathological scores. Pentoxifylline attenuated the accumulation of malonyldialdehyde and transforming growth factor β1 and the activities of myeloperoxidase, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1, and it also restored superoxide dismutase activity. The IP route was more effective than the IR route in this regard. Administration of IP pentoxifylline before or after induction did not influence all parameters. Conclusions: Pentoxifylline showed a therapeutic effect in this experimental colitis model. IP administration seemed to be better. This effect may occur as a result of inhibition of oxidative stress and metalloproteinase activity.