The gastric digestion is the result of physical disintegration and enzymatic reactions leading to the release of nutrients from the food matrix to be absorbed in the upper intestinal tract. Recent works have shown on mini-pig model that the digestion process may be modulated by the initial structure of dairy matrix and suggested that the gastric phase is the critical step. There is a lack of information concerning the microscopic scale of digestion process and the hypothesis most often invoked is that the proteolysis would be limited by the diffusion of gastric fluid into the food, especially pepsin. Nevertheless, fundamental knowledge of gastric digestion had only focused on acid diffusion from the gastric fluid, but no data are currently available for pepsin diffusion. Using fluorescence recovery after photobleaching technique, diffusion coefficients of inactive isothiocyanate (FITC)-pepsin were measured in rennet gels across a range of casein concentrations, modulating different structures of protein aggregates networks. To investigate the microstructural parameters of native gels, electron microscopy image analysis were performed, and then they were qualitatively related to diffusion behavior of FITC-pepsin in these dairy gels. The diffusion coefficients of FITC-pepsin was reduced by a factor 2.4 as the casein concentration of the rennet gels increased from 32.5 to 130 g/kg. Models of polymer science were successfully applied, allowing the reliable prediction of diffusion coefficients calculated from known size of diffusing solutes and physicochemical properties of the food product, e.g. volume fraction, particle size of the gel network. In a more holistic view of food behavior in the human stomach, the diffusion of pepsin should be now confronted with its activity in acidic environment, in order to be able to define more precisely the food particle disintegration mechanisms.