Physical and mechanical properties of the drug-incorporated polymer play a significant role in the release behavior from the drug carriers. Understanding the relative extent of variation in the physical and mechanical properties of the polymer makes it possible to improve the design of polymer carriers to obtain better release profile and increase drug stability. Drug delivery from PLGA loaded with various percentages of diclofenac sodium (DS: 0, 5%, and 10%) at different flow rates of 0 and 7.5 ml/s (flow rate of the healthy internal carotid artery) in phosphate buffered saline (PBS) for different release intervals has been studied. In this research, the change of some physical properties such as free volume fraction, glass transition temperature (Tg) and mechanical properties before and during PLGA release have been investigated. In-vitro release tests have been performed in the PBS medium at the temperature of 37 °C. The results showed that during drug release, Youngs’ modulus and ultimate stress were increased while elongation at break was decreased for different drug loaded films and flow rates. In addition, the zero order kinetic model was found to best fit all the release-profiles obtained.