The main objective of this study was to formulate mesalamine loaded alginate microspheres for local treatment of ulcerative colitis. The microspheres were prepared by ionic gelation method. Box Behnken design using design expert software was employed in formulating and optimizing the microspheres. Microspheres were evaluated for particle size, shape and entrapment efficiency. The drug release of microspheres showed a longer residence time in the colon due to better mucoadhesion properties of sodium ALG. Therefore mesalamine-loaded alginate microspheres can be potential delivery system for local treatment of ulcerative colitis.