Pegylated nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) were prepared by simple solvent displacement method, in the absence of catalysts or specific chemical conditions. Pegylation efficiency increased with the increasing of molecular weight and bulk concentration of poly(ethylene glycols) (PEGs) investigated. In fact, the use of PEG with molecular weight less than 1000 Da did not lead to its attachment. 1H NMR spectroscopy was performed in order to estimate the conformation state of PEG-chains and to predict the nanoparticle structure. Pegylation with PEG 2000 gave surface modified nanoparticles ("brush" conformation), while the chains of PEG 1000 were distributed either in the core or physically adsorbed on the nanoparticle surface. The capacity of nanoparticles to adsorb mucin at pH 7.4 was significantly higher for PEG 1000-NP than for PEG 2000-NP. The "brush" layer seemed to decrease the interaction between PEG 2000-NP and mucin, which facilitated their penetration through the mucus gel. As a consequence, PEG 2000-NP displayed higher capacity to develop adhesive interactions with rat intestinal mucosa in vivo. Independent on the weaker bioadhesive potential of PEG 1000-NP, both types of pegylated nanoparticles demonstrated very high affinity to the intestinal mucosa rather than to the stomach wall, which could be established for drug targeting to the small intestine.