The main aim of the present Investigation was to develop colon targeted matrix tablets of Glipizide using various concentrations of selected polymers are Hydroxy propyl methyl cellulose, Ethyl cellulose and Guar gum. Tablets were prepared by direct compression method and both pre-compression and post- compression parameters for all batches showed the suitable ranges. Short term accelerated stability studies are performed according to ICH guidelines temperature of 400±20 and relative humidity of 75%±5% RH to study any physical changes and chemical decomposition of the drug, in this concern no formulation shown any physical or chemical changes. The compatibility of drugs, polymers and excipients were studied by FT-IR Spectroscopy and the results showed that the drug was compatible with polymers and all excipients. Interaction between drug and optimized formulations were acertain by DSC Thermographs and the results showed that there is no interaction. Dissolution studies were performed for 12 hours in 1. 2 pH, 7.4 pH, 6.8 pH, respectively in phosphate buffer at the temperature of 37±0.50C at 100rpm. The dissolution data so obtained was fitted to various mathematical kinetic models and the drug release followed mixed order and Higuchi’s model. To study release mechanism of the drug from matrices the data were fitted to Koresmeyer-Peppas model. In –vitro release profile of Glipizide from all polymers which are used in study showed that drug increasing the concentration of polymers resulted in a reduction in the release rate of the drug. A formulation containing combination of polymers showed that the drug release profile for Glipizide about 38.72% after 12 hrs, 40.66% after 12 hrs, 45.45% after 12 hrs for all formulations, this is an indicative of the retardation of drug release when polymer combination was changed.