We presents in this work the preparation of several formulations, based on biocompatible biodegradable polymers: polycaprolactone (PCL) and poly(lactic-co-glycolic) acid (PLGA) loaded with Erythromycin (ERYT) antibiotic. These biocompatible materials were used to prepare microspheres with and without immobilized ERYT via simple evaporation method by simple emulsion. The particle size was determined by scanning electron microscopy and the absence of the interaction with ERYT was confirmed via X-ray diffraction and infrared spectroscopy. The release kinetics of ERYT were studied and then, ERYT loaded PCL and PLGA blends microspheres were used for the inhibition of gram-positive S. aureus strain. The microbial activity was carried-out by Agar diffusion disc method. The results show that PCL/PLGA blend and PCL alone inhibited the strain by ERYT present in kinetic aliquots with the complementary effect of the polymers. A numerical model was proposed for modeling the kinetics reported in our study.