Abstract: OBJECTIVE To study the influencing factors of release mechanism of HPMC matix. METHODS Hydrochlorothiazide was selected as a model drug and HPMC as matrix to prepare sustained release tablets, and its release mechanism was described by testing dissolution rate and investigated by the factors of formula and release conditions. RESULTS The release mechanism had the tendency to fit the zero order equation when more HPMC was used and insolubility additives were chosen. When using less HPMC and water-solubility additives, the release mechanism had the tendency to fit Higuchi equation and Ritger-Peppas equation, the release form was the synergistic action of the matrix degradation and drug diffusion. CONCLUSION The types of HPMC used in matrix, the tabletting force, the preparation methods, the assay method of dissolution and rotation speed showed no significant effects on the release mechanism. The content of HPMC, the solubility of additives and the ionic strength of dissolution medium were associated with the release mechanism of hydrochlorothiazide.