Nanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. With the advancement in modern pharmaceutical technologies, Nanotechnology is the one of the most establish technology which is used to improve the therapeutic index and to overcome the formulation challenges of poorly water-soluble compounds. Mesalamine is Anti-inflammatory drug used for the treatment of inflammation of bowel i.e. ulcerative colitis and crohn’s disease. In the present study an attempt is made to formulate the colon targeted drug delivery system of mesalamine using Eudragit -S 100 and HPMC K4M as a release retarding polymer. Various formulations were developed by varying concentration of Eudragit R 100 and HPMC K15M by using wet granulation technique. Developed formulations were evaluated for various parameters like hardness, friability etc. The formulation F3 was found to be optimum based on all evaluation parameters.