Dietary polyphenols have been found to possess preventive and therapeutic potential against several types of cancers. We investigated the effect of ellagic acid on colon cancer induced by 1,2-dimethylhydrazine in rats. Male Wistar albino rats were divided into four groups. Group 1 served as control, group 2 rats received ellagic acid 60 mg/kg bodyweight/every day p.o. throughout the experiment. Rats from groups 3 and 4 were given subcutaneous (s.c.) injections of 1,2-dimethylhydrazine (20 mg/kg body weight) once a week for the first 15 weeks; rats in group 4 received ellagic acid as in group 2 after the last injection of 1,2-dimethylhydrazine and continued till the end of the experimental period of 30 weeks. 1,2-dimethylhydrazine-induced rats exhibited alterations in cancer tumour markers [5'-nucleotidase (5'-ND), gamma glutamyl transpeptidase (gamma-GT), carcinoembryonic antigen (CEA), alphafetoprotein (AFP) and cathepsin-D (CD)]; pathophysiological markers [alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] and oral administration of ellagic acid restored the levels of these marker enzymes. Nuclear factor-kappa B (NF-kappaB) actively involved in the regulation of both pro-inflammatory proteins [inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)] and pro-inflammatory cytokines [tumour necrosis factor (TNF)-alpha and interleukin (IL)-6] and in our study 1,2-dimethylhydrazine-induced group exhibited elevated expressions of all these inflammatory proteins. Ellagic acid administration reduced the expressions of NF-kappaB, COX-2, iNOS, TNF-alpha and IL-6 as confirmed by immunohistochemical, immunoblot and immunofluorescence analysis during 1,2-dimethylhydrazine-induced colon carcinogenesis. In conclusion, ellagic acid demonstrates anti-inflammatory property by iNOS, COX-2, TNF-alpha and IL-6 down-regulation due to inhibition of NF-kappaB and exerts its chemopreventive effect on colon carcinogenesis.