Background Ulcerative colitis (UC) is a recurrent bowel disease. Several medications are used to treat patients with active UC. However, these are associated with side effects that add to the disease-related complications. Aim The aim of the study was to evaluate the therapeutic effect of pentoxifylline, nanocurcumin, and mesenchymal stem cells on experimentally induced UC in rats. Materials and methods Sixty-five adult male rats were divided into six groups: group I was the control group; group II (UC) consisted of rats that received a single intrarectal injection of 2 ml of 4% acetic acid; group ΙIΙ consisted of rats that received a daily oral dose of pentoxifylline starting 3 days after induction of colitis, for 2 weeks; group ΙV consisted of rats that received a daily oral dose of nanocurcumin starting 3 days after induction of colitis, for 2 weeks; group V comprised rats that received a single injection of bone marrow-derived mesenchymal stem cells through the tail vein 3 days after induction of colitis; and group VI consisted of rats that received a single intrarectal injection of 2 ml of 4% acetic acid and were left without treatment for 2 weeks. Colonic samples were processed and examined using histological and immunohistochemical techniques. Results Group ΙIΙ showed improvement in the histopathological picture of colitis. Group IV showed a near-normal histological picture, except for a few areas of surface simple columnar cells that showed discontinuity and a few distorted crypts. Group V showed a histological picture that was nearly similar to that of the control group. Group VI showed a picture that was nearly similar to that of the UC group. There was a significant increase in alcian blue-positive reaction and a significant decrease in the amount of collagen fiber deposition and in tumor necrosis factor α expression (P