Abstract Vagus nerve stimulation of afferents is used as an adjunctive treatment for drug-resistant epilepsy and depression. In addition, anti-inflammatory properties of vagus nerve stimulation have been reported in various experimental models of inflammation but not in colitis. These effects are thought to be mediated via peripheral release of acetylcholine from the vagus and subsequent activation of macrophages. Our aim was to evaluate in rats the anti-inflammatory effects of chronic vagus nerve stimulation on colonic inflammation. Colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid. Vagus nerve stimulation (left cervical) was performed in freely moving animals 3 h per day for five consecutive days. Assessment of colonic inflammation was obtained using physiological (e.g. body weight, temperature and locomotor activity) parameters, macroscopical (area of lesions), histological, and biological parameters (e.g. myeloperoxidase activity, cytokine and cytokine-related mRNAs), both at the level of the damaged colon and the colon immediately above. A global multivariate index of colitis was then generated for a better characterization of colonic inflammation. Vagus nerve stimulation reduced the degree of body weight loss and inflammatory markers as observed above the lesion by histological score and myeloperoxidase quantification. This anti-inflammatory effect was also demonstrated by the improvement of the multivariate index of colitis. These data argue for an anti-inflammatory role of vagus nerve stimulation chronically performed in freely moving rats with colitis and provide potential therapeutic applications for patients with inflammatory bowel diseases.