A gastro-resistant system of acryl-EZE® MP coated alginate/chitosan microparticles was developed to improve the controlled release of oxytetracycline (OTC). Microparticles were obtained by complex coacervation and, thereafter, were coated using fluidized polymer dispersion with acryl-EZE® MP solution. OTC distribution inside the microparticles was determined by multiphoton confocal microscopy, demonstrating the efficiency of encapsulation process. In vitro OTC release kinetic was performed in order to obtain the release profile in gastric and intestinal simulated fluids. A fast initial release, or burst effect, was observed with uncoated microparticles loaded with OTC in gastric conditions. When a 50% mass increase in acryl-EZE® MP coating was achieved, OTC release in acidic medium was greatly reduced, resulting in the expected gastro-resistant effect. Different mathematical models were applied to describe the drug diffusion across the polymer matrix. The Logistic model was the best tool to interpret the experimental data in most of the systems studied. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40444.