Layer-by-layer adsorption of oppositely charged polyelectrolytes has been used for the manufacturing of hollow microspheres or capsules for controlled release studies. Using this self-assembly technique, microsphere core material was encapsulated with poly styrenesulfonate (PSS) and poly allylamine (PAH) multilayers or PAH and polyvinyl sulfate (PVS) multilayers and the core dissolved to produce hollow microcapsules. The microspheres were loaded with fluorescein-isothiocyanate (FITC)-labeled dextran of different molecular weights for different lengths of time to quantify the release properties. After loading, the capsules were immersed in water and the FITC-dextran was allowed to diffuse into the mother liquor. The FITC-dextran concentration of the mother liquor was measured over a period of hours and days. In this study, one- and two-compartment models were developed, based on a species mass balance, to predict the concentration of dextran release from the microcapsules over time. The two-compartment model was found to be superior to the one-compartment model in its fit to the observed data. The model was applied to experimental data in order to characterize the release properties of microcapsules with different numbers of layers and constituent architectures.