This study investigated whether various dietary fats affected the Wnt signaling pathway of preneoplastic lesions of colon mucosa in acrylamide (ACR)-treated rats. Male Sprague-Dawley rats were given intraperitoneal injections of ACR at a dose of 5 mg/kgbw and diets supplemented with 10% corn, olive, beef, or fish oil for 8 weeks; and then rats were still fed with diets supplemented with 10% oil for other 40 weeks. Aberrant crypt foci (ACF) were examined at 12 weeks post-ACR-exposure. At 48 weeks, normal appearing colon mucosal proliferation and apoptosis were evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and percentages of fragmented DNA, respectively; the expressions of beta-catenin, cyclin D1, Wnt2, Wnt3, and Wnt5a of normal appearing colon mucosa were analyzed by Western blot analysis. Results from this study showed that long-term exposure of rats to dietary corn oil and beef tallow enhanced ACF formation in ACR rats. In contrast, olive and fish oil weakened the ACF formation. Dietary corn oil and beef tallow increased BrdU incorporation, expression of cytosolic beta-catenin and cyclin D1; and decreased apoptosis in the colon mucosa of ACR rats. ACR rats fed beef tallow showed increased expressions of Wnt2 and Wnt3. ACR rats fed corn oil showed increased expressions of Wnt5a. These findings suggest that long-term high intake of corn oil and beef tallow enhanced, whereas olive and fish oil weakened cell proliferation through Wnt signaling, which might contribute to promoting effects in preneoplastic lesions of colon mucosa.