The mechanism of tissue damage in ulcerative colitis (UC) is unknown. However, recent evidence suggests that reactive oxygen species (ROS) are critical mediators of inflammation, and tissue damage in UC and antioxidants could be beneficial in the treatment of UC. Our aim was to evaluate the effects of two new antioxidants, Zolimid and AEOL11201 on experimental colitis. Antioxidants or vehicle were given to rats for five days after induction of colitis by intrarectal administration of 4% acetic acid. Severity of colitis was assessed on day 5. Zolimid and AEOL11201 significantly improved acetic acid-induced colitis. Both Zolimid and AEOL11201 significantly decreased the severity of diarrhea, and severity of macroscopic and histological changes in the colon. Both agents also significantly decreased colonic MPO levels. In conclusion, Zolimid and AEOL11201 are effective antiinflammatory agents in an animal model of colitis. Further studies are needed to evaluate their beneficial therapeutic effects in patients with UC.