Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,llactic acid) block copolymers (Me.PEG–PLA) or blends of Me.PEG–PLA and PLA by the precipitation–solvent diffusion method. These nanoparticles, labeled by introducing [14C]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG–PLA nanoparticles that were intravenously administered to rats is increased by a factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear phagocytes system avoidance was explained according to a conformation model in which the PEG density at the surface of the particles is a key parameter.