Abstract: AIM：To study the influence of hydration and gelation of hydroxypropyl methyl cellulose (HPMC) in different medium on drug release from HPMC matrices. METHODS: Tablet press method was used to obtain the tranilast sustained-release (Tra-SR) tablet matrices consisting of hydroxypropyl methylcellulose (HPMC K_4m) and pure HPMC tablet. The weights and dimensions of the HPMC tablets and the Tra-SR tablets were measured using gravimetric method and micrometer screw gauge prior to hydrating and swelling determination in simulated intestinal fluid (SIF, pH 7.3) and simulated gastric fluid (SGF, pH 1.3) at definite time, respectively. RESULTS: For HPMC tablets, the hydrating rate constants are 0.897 h^-1 in SGF and 0.681 h-1 in SIF; the swelling rate constants are 1.005 h^-1 in SGF and 0.713 h^-1 in SIF. For the Tra-SR tablets, in SGF its weight and dimension increased quickly in the first half-hour and then decreased slowly; but in SIF it increased slowly with prolongation of the immersion within 5 hours and then its dimension remained constant. CONCLUSION: The extent and velocity of hydrating and swelling of matrix were affected by the pH of the dissolution medium and period of time. The erosion of gel layer is a rate control factor for tranilast release from HPMC matrix sustained release tablet.