The etiology and pathogenesis of inflammatory bowel disease are still not fully understood. However, evidence from both animal models and clinical observations suggests luminal bacteria as the most probable inducer of this disease. The intestinal bacterial microbiota may be modified by dietary addition of viable probiotic bacteria, thereby constituting an alternative approach to disease prevention and treatment. The aim of this study was to evaluate and compare the effects of two probiotic regiments; Lactobacillus GG and a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium lactis (YO-MIX Y 109 FRO 1000) in both normal and trinitrobenzenesulfonic acid colitis-induced rats. Colon morphology and damage were evaluated histologically; colonic tissues were used for mRNA analysis, using real-time PCR. Administration of both probiotics reduced the expression of proinflammatory cytokines tumor necrosis factor-alpha and IL-6 and increased the expression of mucin 2 in compared with colitis group and reduced the inflammatory response. These results provide additional support for the positive effect of probiotics in the gut and may shed light on the mechanism by which probiotic bacteria exert their action in an animal model.