Scope: The food contamination by mycotoxins is of increasing public health concerns. Deoxynivalenol (DON), a mycotoxin contaminating cereals has been associated with the exacerbation of inflammatory bowel diseases (IBD), thereby raising the question of its role in the development of IBD. Moreover, the effect of DON on the colon is poorly described. Methods and results: Wistar rats exposed (1-4 weeks) to low doses of DON (2 or 9 mg.kg-1 feed) showed microscopic alterations of colonic tissue (dilated lymphatic vessels, luminal debris, and cubic and flattened enterocytes). Ingestion of DON also altered colonic functions by increasing paracellular permeability while reducing the expression of the tight junction proteins and increased apoptosis in colonic tissue. Pro-apoptotic factors Bax/Bak, cytochrome C and caspase 9 were upregulated whereas expression of anti-apoptotic protein Bcl2 tended to decrease for the mitochondrial pathway. An increased expression of FasR and caspase-8 was observed for the extrinsic pathway. An increase in the pro-inflammatory markers TNFα, IL-17 and myeloperoxidase was also observed. Conclusion: These results indicate that the dietary exposure to low levels of DON in food targets the colon inducing a health-threatening breakdown of the colonic barrier, highlighting oral exposure to DON as a potential risk factor in triggering IBD.