Heavy oil fractions can be upgraded through various processes, such as catalytic residue hydrotreatments. Mass transfer of macromolecules present in the heavy oil fraction, so-called asphaltenes, from feedstock to catalytic active sites is limited during hydroprocesses. Mechanisms of the diffusion of asphaltenes through pore network, adsorption, and pore plugging are no well-known under process conditions. A new method has been developed to characterize and investigate asphaltene diffusion phenomenon in catalysts under a high temperature and pressure. Alumina supports immersed in asphaltene solution are left to evolve at 250 degrees C and 5.0 MPa. Solutions and supports are analyzed to quantify the mass transfer, penetration depth, and change in support porosity of asphaltenes. This procedure was evaluated in terms of reproducibility and sensitivity. The impact of several parameters, such as pressure, was appraised. With this powerful procedure, for the first time, asphaltene diffusion without conversion into the pore network of a catalyst at a high temperature and pressure has been monitored over time. In accordance with analytical results, we proposed a primary model for the asphaltene adsorption and pore network cluttering mechanism under hydroprocessing conditions.