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The uptake of lysozyme by oppositely charged poly(acrylic acid) microgels was investigated by micromanipulator-assisted light microscopy and confocal microscopy. Lysozyme was observed to distribute nonuniformly within the microgels, forming a core-shell structure with considerably higher lysozyme concentration in the shell than in the core. The core-shell formation can be divided into two periods. During the first of these, the shell is formed during rapid microgel deswelling, and with no lysozyme diffusing into the microgel core. This is followed by a second period, during which microgel deswelling is negligible and lysozyme diffuses into the microgel core. Thus, the shell which is initially formed as a result of fast lysozyme transport to the gel network and fast protein-microgel interactions is able to carry a mechanical load and prevents deswelling during the latter core diffusion period. These two distinct regimes of lysozyme loading were also successfully described theoretically, demonstrating the importance of lysozyme cluster formation for the observed phenomena.