The aim of the present study was to develop and characterize an oral sustain release drug delivery system for commonly prescribed antipsychotic Quetiapine fumarate. Hydrophilic matrix based tablets using different concentrations of different grades of hydroxypropyl methylcellulose (HPMC) viz. K100 LV and K4M CR was developed using wet granulation technique. The prepared tablets were of 50mg dose and were designed for oncedaily administration. The formulations prepared were evaluated for the release of Quetiapine fumarate over a period of 24 hrs. using USP type II dissolution test apparatus. The prepared tablets were evaluated for physical properties. The in- vitro drug release studies revealed that the tablets containing 15% of HPMC K4M CR of the total tablet weight showed satisfactory results and was able to control the release over 22 hrs. Further the influence of commonly used excipients viz. Lactose, MCC and Starch 1500 was studied on the selected formulation. The invitro release data of prepared formulations followed Korsmeyer- Peppas and Higuchi kinetics strongly. The selected formulation was compared with the marketed product for the drug release pattern and was matched using similarity factor (f2) above 50. In conclusion, the dissolution profiles and the mathematical model fittings indicate that release of Quetiapine fumarate can be effectively controlled by use of hydrophilic matrix systems.