The aim of the present study was to investigate the chemoprotective activity of anthocyanin-rich extracts (AREs) from bilberry (Vaccinium myrtillus L.), chokeberry (Aronia meloncarpa E.), and grape (Vitis vinifera) by assessing multiple biomarkers of colon cancer in male rats treated with a colon carcinogen, azoxymethane. Fischer 344 male rats were fed the AIN-93 diet (control) or AIN-93 diet supplemented with AREs for 14 wk. Biomarkers that were evaluated included the number and multiplicity of colonic aberrant crypt foci (ACF), colonic cell proliferation, urinary levels of oxidative DNA damage, and expression of cyclooxygenase (COX) genes. To assess the bioavailability, levels of anthocyanins in serum, urine, and feces were evaluated. Total ACF were reduced (P<0.05) in bilberry, chokeberry, and grape diet groups compared with the control group. The number of large ACF was also reduced (P<0.05) in bilberry and chokeberry ARE-fed rats. Colonic cellular proliferation was decreased in rats fed bilberry ARE and chokeberry ARE diets. Rats fed bilberry and grape ARE diets had lower COX-2 mRNA expression of gene. High levels of fecal anthocyanins and increased fecal mass and fecal moisture occurred in ARE-fed rats. There was also a significant reduction (P<0.05) in fecal bile acids in ARE-fed rats. The levels of urinary 8-hydroxyguanosine were similar among rats fed different diets. These results support our previous in vitro studies suggesting a protective role of AREs in colon carcinogenesis and indicate multiple mechanisms of action.