Background: Anacardium occidentale L. is a tropical plant used for the treatment of inflammatory diseases. The goal of the present work was to investigate the anti-inflammatory and anti-oxidant potential of oral administration of cashew nuts (from Anacardium occidentale L.) in a mouse model of colitis. Methods: Induction of colitis was performed by intrarectally injection of dinitrobenzene sulfonic acid (DNBS). Cashew nuts were administered daily orally (100 mg/kg) in DNBS-injected mice. Results: Four days after DNBS, histological and macroscopic colon alterations as well as marked clinical signs and increased cytokine production were observed. Neutrophil infiltration, measured by myeloperoxidase (MPO) positive immunostaining, was correlated with up-regulation of adhesion molecules ICAM-1 and P-selectin in colons. Oxidative stress was detected with increased malondialdehyde (MDA) levels, nitrotyrosine, and poly ADP-ribose polymerase (PARP) positive staining in inflamed colons. Oral treatment with cashew nuts reduced histological, macroscopic damage, neutrophil infiltration, pro-inflammatory cytokines and MDA levels, as well as nitrotyrosine, PARP and ICAM-1, and P-selectin expressions. Colon inflammation could be related to nuclear factor (NF)-kB pathway activation and reduced manganese superoxide dismutase (MnSOD) antioxidant activity. Cashew nuts administration inhibited NF-kB and increased MnSOD antioxidant expressions. Conclusions: The results suggested that oral assumption of cashew nuts may be beneficial for the management of colitis.