Abstract Dietary fiber (DF), the fermentation substrates for colonic bacteria, has acquired a crucial status in protection against colorectal cancer. DF consists of mucilage, beta-glucans and pectin (soluble fiber) and cellulose, hemicelluloses and lignin (insoluble fiber) which, are cross-linked with proteins and phenolic compounds. DF improves optimal health through fecal quality, quantity and decreased carcinogenic colonic bacterial metabolites. One of the physico-chemical properties of DF attributed to these important health functions is the natural presence of salicylic acid (SA), an active component of Aspirin in our foodstuffs. However, the presence of SA has been recently reported to be gradually diminishing from our foodstuffs as a result of manmade activity. A large number of studies support the effectiveness of Aspirin in inhibition of colorectal cancer cells growth in-vitro and in-vivo. DF is not currently fortified with Aspirin, nor have the effects of Aspirin fortification on physico-chemical properties of DF been thoroughly studied. Of note, gastrointestinal bleeding is one of the effects associated with high dose aspirin use. This research aims to assess the efficacy of fortification of DF-rich foodstuffs with Aspirin in-vivo using the N-methyl-N-nitrosourea carcinogen-induced model of colorectal cancer in rats, with emphasis on the mechanism of biologic action. A total of 30 male Albino rats whose weight falls between 110-150g were used. They were grouped into 6 sets of 5 rats each and a soluble and insoluble DF feeding intervention was systematically employed in various combinations with Aspirin (1600mg/kg diet) and without Aspirin fortification for 80 days. NMU was administered at a dose of 2 mg/kg intra rectally every other day for 60 days until the development of colorectal cancer which, was confirmed by barium enema and histological analysis. Hemogram and other pertinent investigations were done ultimately including histological assessment of tumors. The tumors were processed for histological analysis and immunohistochemistry using Anti-p53 and Anti-Bcl-2 antibodies. Findings show no histologically detectable colorectal tumor in the group of rats fed with Aspirin-fortified mixture of soluble and insoluble DF foodstuffs. There was a considerable tumor regression in the group fed with Aspirin-fortified soluble/insoluble DF when compared to non-fortified group. The results show up-regulation of p53 and down-regulation of Bcl-2 proteins in Aspirin-fortified DF fed rats when compared with non-fortified group (p <0.05). These results imply that DF fortification with Aspirin at low dose may serve as a possible preventive measure against colorectal cancer especially in tumor prone individuals. There is a need for further research. Note: This abstract was not presented at the conference. Citation Format: Mohammed Faruk, Abdulmumini Hassan Rafindadi, Sani Ibrahim, Surajo Mohammed Aminu, Ahmed Adamu, Yawale Iliyasu, John Idoko, Mohammed Sani Shehu, Adamu Abdullahi, Abdullahi Jubril Randawa, Atara Ntekim, Saad Aliyu Ahmed, Cheh Augustine Awasum, Kasimu Adoke, Andrew Jonathan Nok. Fortification of dietary fiber-rich foodstuffs with Aspirin and its effect on colorectal carcinogenesis in rats. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A27.