The purpose of this study was to compare the effect of carbohydrate structure and digestibility on azoxymethane (AOM)-induced colon carcinogenesis. Five groups of male Fischer 344 rats each comprising 30 animals were injected with AOM and fed a high-fat diet with 15% of various carbohydrates. The carbohydrate sources used were sucrose, cornstarch (a linear starch, reference group), potato starch (a branched starch), a short-chained oligofructose (Raftilose®), and a long-chained inulin-type fructan (Raftiline®). An interim sacrifice was performed after 9 wk to investigate markers of carbohydrate digestibility, including caecal fermentation (caecum weight and pH) and glucose and lipid metabolism [glucose, fructoseamine, HbA1c, triglycerides, and insulin-like growth factor (IGF) 1]. In addition potential early predictors of carcinogenicity [cell proliferation and aberrant crypt foci (ACF)] at 9 wk and their correlation to colon cancer risk after 32 wk were investigated. Tumor incidence was significantly reduced in animals fed oligofructose, and the number of tumors per animal was significantly reduced in animals fed inulin and oligofructose at 32 wk after AOM induction compared to the reference group fed sucrose. Increased caecum weight and decreased caecal pH were seen in groups fed oligofructose, inulin, and potato starch. Plasma triglyceride was decreased in rats fed oligofructose and inulin. Cell proliferation was increased in the proximal colon of rats fed sucrose, oligofructose, and inulin, and the number of cells per crypt decreased in rats fed oligofructose and inulin. The total number of ACF's was unaffected by treatment, and the size and multiplicity of ACF was unrelated to tumor development. It was concluded that less digestible carbohydrates with an early effect on caecum fermentation and plasma triglyceride decreased subsequent tumor incidence and multiplicity. This was unrelated to ACF, cell proliferation, and other markers of glucose and lipid metabolism.