The aim of this study was to investigate the potential of pioglitazone hydrochloride as a promising anticancer agent and then to design and evaluate the colon-targeted delivery system. The role of pioglitazone hydrochloride as a promising anticancer agent was evaluated by in vitro cell line studies and in vivo 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. In order to deliver the drug at site of action, i.e. colon, drug embedded in matrices containing a release retarding polymer (HPMC K4M) and a polysaccharide (locust bean gum) were prepared. These matrix systems were further enteric coated with Eudragit®S100 to minimize the premature drug release in the upper segments of the GIT. In vitro dissolution studies were performed in absence and presence of rat caecal contents on selected batches and samples were analyzed using a validated RP-HPLC method. Hence, the studies led to the conclusion that successful site-specific delivery systems of pioglitazone hydrochloride were developed to improve its therapeutic efficacy in the management of colorectal cancer.