Many epidemiological studies have demonstrated that level of exercise is associated with reduced colorectal cancer risk. Treadmill training can decrease Apc^Min/+ mouse intestinal polyp number and size, but the mechanisms remain unclear. Understanding the molecular changes in the tumor following exercise training may provide insight on the mechanism by which exercise decreases Apc^Min/+ mouse polyp formation and growth. The purpose of this study was to determine if exercise can modulate Apc^Min/+ mouse intestinal polyp cellular signaling related to tumor formation and growth. Male Apc^Min/+ mice were randomly assigned to Control (n=20) or Exercise (n=20) treatment groups. Exercised mice ran on a treadmill at a moderate intensity (18 m/min, 60 min, 6 d/wk, 5% grade) for 9 weeks. Polyps from Apc^Min/+ mice were used to quantify markers of polyp inflammation, apoptosis, and -catenin signaling. Exercise decreased the number of macrophages in large polyps by 35%. Related to apoptosis, exercise decreased the number of TUNEL positive cells by 73% in all polyps. Bax protein expression in polyps was decreased 43% by exercise. B-catenin phosphorylation was elevated 3.3-fold in polyps from exercised mice. Moderate-intensity exercise training alters cellular pathways in Apc^Min/+ mouse polyps and these changes may be related to the exercise-induced reduction in polyp formation and growth.