We found that voluntary running wheel exercise inhibited small intestinal tumor formation in female ApcMin/+ mice and colon tumor formation in AOM/DSS-treated male CF-1 mice, and the inhibitory effect may be associated with decreased IGF-1/IGFBP-3 ratio as well as aberrant β-catenin signaling and arachidonic acid metabolism. The gene discussed is IGFBP3; the disease is colonic neoplasm.