Probiotics (PB) are living microorganisms that act as a commensal population in normal intestines and confer numerous beneficial effects on the host. The introduction of probiotics in the treatment of inflammatory bowel disease (IBD) prolongs remission. The aim of this study was to investigate the intestinal and hepatic effects of PB supplementation in an experimental IBD model in mice induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the first step of the experimental procedure, CD-1 male mice, 5 to 6 weeks old, were randomly divided into 3 groups and inoculated intrarectally with, respectively, saline, alcohol, or TNBS to assess the experimental IBD model. In the second step, mice treated, or not, with TNBS inoculation, were treated with PB (Lactobacillus Casei, Bifidobacterum Lactis) for 1, 2 or 3 weeks, on a daily basis. Large bowel (colon and rectum) and liver were processed for histological alterations, according to a scoring system. Large bowel was also assessed for apoptosis by TUNEL assay. TNBS induced, as expected, severe damage and inflammation in the large bowel, including nuclear alterations and apoptosis, and, to a lesser extent, to the liver. Administration of PB determined significant reduction of both histological alterations and apoptosis. PB administration in advance protects from inflammation. In conclusion, supplementation with Lactobacillus casei, Bifidobacterum lactis PB is able to ameliorate the colitis by reversing the histological changes caused by TNBS in mice. Experimentation in human subjects in needed to prove their efficacy in reducing histological alterations that may be present in subjects with IBD.