In the field of drug delivery systems, microparticles made of polymeric matrix appear as an attractive approach. The in vitro release kinetic profile is crucial information when developing new particulate formulations. These data are essential for batch to batch comparison, quality control as well as for anticipation of in vivo behavior to select the best formulation to go further in preclinical investigations. The methods available present common drawbacks such as the time- and compound-consumption that does not fit with formulation screening requirements in early development stages. In this study, a new microscale high throughput screening (HTS) method has been developed to investigate drug release kinetic from piroxicam-loaded polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA) microparticles. The method is a sample- and separation-based method where separation is performed by filtration using 96-well micro filter plates. 96 experiments can therefore be performed on one plate in one time in a fully automated way and with a very low sample and particle consumption. The influence of different parameters controlling release profiles was also investigated using this technique. The HTS method gave the same release profile than the standard dialysis method. Shaking, particle concentration, and the nature of the release medium were found to be of influence. The HTS method appears as a reliable method to evaluate drug release from particles with smaller standard deviation and less consumption of material.