The present study examines the effect of multimedia dissolution profile on the drug release of sustained release hydrophilic matrices of metformin hydrochloride containing combination of different grades of hydroxypropyl methylcellulose. Metformin HCL, the only available biguanide, remains the first line drug therapy for patients with Type 2 diabetes mellitus acts by decreasing hepatic glucose output and peripheral insulin resistance. It has relatively short plasma half-life and low absolute bioavailability. Hydrophilic matrices were prepared using combination of different grades of HPMC viz. HPMCK4M and HPMCK15M to sustain the release of the drug. Multimedia dissolution studies were performed to mimic the in-vivo condition by doing in-vitro test. The pH/buffer selection is based on the exposure of drug from stomach to intestine/colon. The study ensures the impact of pH changes on dissolution and release of drug substance for absorption. Hydrophilic matrices of metformin hydrochloride also provide quite regulated release of the drug over an extended period of time.