Colon cancer is the third most common malignant neoplasm in the world and it remains an important causeof death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), isalso a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemicallyinduced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TAagainst DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated interms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changesand expression of early molecular markers of inflammation and tumor promotion. DMH treatment inducedoxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons ofWistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanismthat involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-α(p<0.001) release. It could be concluded from our results that TA markedly protects against chemically inducedcolon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.