The aim of the study was to investigate the effect of the size and PEG coating density of Poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nano- and microparticles on their transport across the nasal mucosa. Particles were made of PLA-PEG copolymers of two different molecular weights (Mw: 37 and 28 kDa) and also PLA of Mw 28 kDa, and prepared using different techniques (simple emulsion (o/w), double emulsion (w/o/w), and nanoprecipitation techniques). The particles were characterized for their size, zeta potential, morphology [Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM)], and PEG coating efficiency. Additionally, the transport of rhodamine 6G-labelled PLA-PEG and PLA particles across the rat nasal mucosa was investigated by Confocal Laser Scanning Microscopy (CLSM). The results showed that the size of PLA-PEG nanoparticles varied between 150 and 300 nm and their zeta potential between -10 and -22 mV depending on both the polymer Mw and the preparation technique. Moreover, the PEG coating efficiency (amount of PEG on the surface with respect to the total amount of PEG in the particles) was high (between 75% and 92%) and affected by the PLA Mw and also by the particles preparation technique. The greatest PEG surface density was achieved for lowest Mw PLA-PEG, using the O/W emulsification technique. The CLSM images of nasal epithelia from rats showed the importance of the PEG coating density and the size on the transmucosal transport of the fluorescent nanoparticles. More specifically, PLA-PEG particles with a high PEG coating density and a small size were more significantly transported than noncoated PLA nanoparticles and also than PLA-PEG nanoparticles with a lower coating density. In conclusion, these results showed the important role that the PEG coating has on the efficacy of PLA-PEG nanoparticles as nasal drug carriers.