High-sucrose consumption is associated with increased risk of human colon cancer. Our previous research indicated that high-sucrose diets (vs. cornstarch) promote intestinal epithelial cell proliferation and tumorigenesis as well as increase serum glucose and hepatic IGF-I mRNA levels in APC(Min) mice. To examine the role of functional pathways, in particular of IGF-I signaling, in sucrose-induced intestinal epithelial cell proliferation and tumorigenesis, we examined the effects of dietary carbohydrate source (sucrose vs. cornstarch) on gene expression in the intestinal epithelium using cDNA microarray and quantitative RT-PCR analysis. Dietary carbohydrate source significantly (P < 0.05) altered mRNA expression of 109 known genes in the small intestinal epithelium, including many involved in metabolic pathways. Consumption of high-sucrose diets altered expression levels of genes involved in cell adhesion, cell cycle control, and transduction signaling, consistent with increased risk of intestinal tumorigenesis. High-sucrose intake also affected expression of genes involved in IGF-I signaling, including upregulating IGF-II and downregulating IGFBP3, which supports our hypothesis that IGF-I signaling could play a role in intestinal epithelial cell proliferation and tumorigenesis promoted by high-sucrose consumption.