The kinetics of uptake and release of fluorescently labeled lysozyme by/from spherical oxidized starch polymer microgel particles (diameter 10–20 µm) was investigated using confocal laser scanning microscopy. Both the protein and the microgel have a pH dependent charge; in the pH range 3–9, the protein (pI ˜ 10) is positive and the gel is negative. Uptake was monitored at different protein concentrations, pH values and ionic strengths. Lysozyme release was triggered by changing the pH and salt concentration and measured during enzymatic degradation of the gel by a-amylase. The release is of importance for potential use of the microgel in gastro-intestine drug delivery applications, while amylase-induced protein release is relevant for antimicrobial applications. To analyze the uptake and release kinetics we used a model based on diffusion, taking into account equilibrium exchange between protein bound to the gel matrix and free protein in the gel. For the uptake process the time-dependent evolution of the protein concentration profile in the gel phase and the medium was computed numerically. The calculated concentration profiles closely resemble the experimentally found profiles. In the case of high affinity between protein and the gel network (at low pH and low ionic strength), the initial uptake rate equals the limiting flux of protein at the gel–solution interface, completely determined by the rate of diffusion in the medium. The diffusion coefficient of free protein in the gel, Dp,g, was found to be on the order of 10-11 m2 s-1, about one order of magnitude lower than the diffusion coefficient of lysozyme in bulk solution. Release experiments were carried out with zero protein concentration in the medium, for which approximate analytic release equations are available. The experimental release curves obtained at pH 7 yielded estimated values for the concentration ratio R of bound and free protein in the gel and, related to this ratio, the effective diffusion coefficient of lysozyme in the gel, Deff. These values are extremely dependent on the ionic strength, ranging from ca. 1000 and 10-14 m2 s-1 at 0.025 M NaCl to 50 and 2 × 10-12 m2 s-1 at 0.05 M, respectively. The results are in line with our earlier absorption and FRAP (fluorescence recovery after photobleaching) studies, showing a sharply decreasing affinity and increasing overall exchange rate with increasing ionic strength. Amylase completely breaks down the oxidized starch microgel, while releasing the embedded protein into solution.