A composite hydrodynamic-diffusion model of the arterial wall is presented to describe the vesicular transport of relatively inert macromolecules across the inner endothelial lining of the larger arteries of humans and animals and their subsequent diffusion in the underlying tissue of the intima and media. This model is motivated by the highly specialized ultrastructure of the arterial wall observed in electron microscopic studies and the recent experimental measurements of the time-dependent uptake of labelled macromolecules in animal arteries under carefully controlled in vitro conditions. The proposed dynamic model for the vesicular transport across the endothelial cell layer considers the constrained Brownian diffusion of 700 Å vesicles subject to long-range hydrodynamic and short-range London-van der Waals force interactions with the plasmalemma membranes of the endothelial cell. Approximate solutions are developed for the motion and the steady-state vesicle density distribution near the plasmalemma and in the interior of the cell using boundary-layer-like methods. The model for the vesicular transport just described appears as a novel boundary condition in the basic diffusion model for the underlying tissue. The latter is treated as a two-phase medium comprised of an interstitial fluid continuum with a uniformly dispersed smooth muscle phase as first proposed by Hills (1968). This model for the underlying tissue assumes that the smooth muscle cells contribute insignificantly to the macromolecule diffusion across the arterial wall but act as the principal storage reservoir for the macromolecules for large diffusion times because of their large volume fraction. The dimensionless parameters that arise in the theoretical model are determined by comparing the solutions for the time-dependent total wall uptake with Fry's (1973) experimental data for canine carotid artery.