The objective of this research was to prepare a Gastro Retentive drug delivery system (GRDDS) of Diltiazem hydrochloride. In the present study, preparation of Diltiazem HCl Microspheres was formulated using Eudragit RL100 and Eudragit RS100 as the rate controlling polymer, alone by solvent evaporation methods with an aim to prolong its release. Six formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters. Particle size analysis, drug encapsulation efficiency, Invitro release studies were performed. The mean particle size of prepared hollow microspheres increased but the drug release rate from the microspheres decreased as the polymer concentration increased. Depending upon the drug to polymer ratio, the entrapment efficiency were found to range between 97.73± 0.27, 91.28± 0.38, 95.8± 0.25, 85.21± 0.36, 87.84± 0.27, 88.12± 0.28 respectively. In-vitro evaluation of Floating Drug Delivery System (FDDS), prediction of the drug release, and polymers concentration to match target release profile was investigated. In vitro studies were carried out at different pH for a period of 12 hours. The scanning electron microscopic study indicated that the microspheres were spherical in shape and the drug remained dispersed in the polymer matrix at amorphous state. Drug polymer interaction was absent as evidenced by FT-IR.