The Western diet is commonly consumed by industrialized societies and characterized by an increased consumption of vegetable oils rich in omega-6 (n-6) fatty acids. This results in a higher ratio of omega-6 to omega-3 (n-3) fatty acids in the diet. Omega-6 polyunsaturated fatty acids (PUFA) are believed to induce a pro-inflammatory response in the body. Therefore, this change in PUFA concentration and/or ratio of n-6:n-3 in the Western diet may contribute to colorectal cancer (CRC) risk. Five identical diets, varying only in PUFA concentration and n-6:n-3 ratio, were fed to mice dosed with a carcinogen and an inflammatory accent (AOM+DSS). The diets included: 1.) AIN-93G, control diet, containing 7% (kcal) dietary PUFA, 7:1 n-6:n-3 ratio, 2.) 2.5% dietary PUFA 1:1 n-6:n-3 ratio, 3.) 2.5% PUFA 20:1 n-6:n-3, 4.) 10% PUFA 1:1 n-6:n-3, and 5.) 10% PUFA 20:1 n-6:n-3. PUFA ratio had a significant effect on tumor size. Diets having an n-6:n-3 ratio of 1:1 resulted in significantly larger tumors than diets with an n-6:n-3ratio of 20:1. Mice fed either the AIN-93G or 2.5% 1:1 diet had the highest number of tumors compared to the other experimental diets. From these results, it appears that the dietary PUFA profile influences the etiology of CRC. Studies investigating CRC commonly use rodent models to investigate human diseases. Typically rodents are fed diets formulated to promote growth and heath, however these diets are considerably different than the Western diet in terms of macro- and micronutrients. Diet is known to influence CRC incidence, which led to the development of the Total Western Diet (TWD) by Hinze and colleagues. The TWD is a rodent diet that uses purified ingredients to match the macro- and micronutrient composition of the average American diet. However, the complex nature of whole-foods is also known to impact colon health, so the TWD was redesigned. The TWD-2 is the only whole-foods-based rodent diet that emulates the macro- and micronutrient consumption of the average American. Initiating studies using the TWD-2, in place of the AIN diets, will hopefully make the rodent a better model for human disease research.