Ulcerative colitis is known to cause damage to the liver tissue. Although synthetic and natural substances have been used to prevent liver damage in colitis, little success has been achieved so far. In this study rats were given 120 mg/kg of trinitrobenzene sulfonic acid (TNBS) in order to induce colitis. Protective effects of lycopene and N-Nitro-L-Arginine Methyl Ester (L-NAME) on oxidative stress and liver damage in colitis were assessed. 91 male Sprague Dawley rats were used in this study. These rats were divided into 12 groups, each consisting of 7 rats, apart from the control group. 1ml of saline was administrated intraperitoneally (i.p) to the rats in the control group, while all the other groups were given TNBS dissolved in 50% ethanol through the intrarectal tract on the first day of the experiment. Groups 1, 2 and 3 were labeled as TNBS groups. 24 hours after the administration of TNBS, rats in groups 4, 5 and 6 were given L-NAME, the ones in groups 7, 8, 9 given 1 ml/kg olive oil. The remaining groups (10, 11 and 12) were given 5 mg/kg of lycopene i. p. Histological and biochemical analyses were carried out. In liver, tissue damage parameters like edema, sinusoidal dilatation, necrosis, vacuolization and accumulation of inflammatory cells were observed. Evaluation of serum aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels, as well as histopathological findings of the liver tissue, show that lycopene has a protective effect upon liver damage due to colitis, and that lycopene is more beneficial to preventing oxidative stress than are olive oil and L-NAME, a synthetic antioxidant substance.