The present work is aimed at investigating the release of Diclofenac (DCF) from Eudragit RS100 (RS) microparticles to a biological model membrane consisting of dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV). The microparticles were prepared by the Quasi-Emulsion Solvent Diffusion method (QESD). The drug release was monitored by Differential Scanning Calorimetry (DSC) technique, following the effects exerted by DCF on the thermotropic behaviour of DMPC multilamellar vesicles at different temperatures. DCF affects the transition temperature (Tm) of phospholipid vesicles, causing a shift towards lower values, which is modulated by the drug fraction entering into the lipid bilayer. Calorimetric measurements were performed at two different pH (4.0 and 7.4) on suspensions of blank liposomes added to weighed amounts of unloaded and DCF-loaded microspheres, as well as to the powdered free drug, after incubation at 37 degrees C. The Tm shifts, caused by the drug released from the polymeric system or by the free drug during incubation cycles, were compared to those caused by a chosen molar fractions of the free drug dispersed directly in the membrane. This in vitro study suggests as the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres as well as by the pH value, acting on drug solubility and membrane disorder.