The aim of the present work was to assess the merits of PEGylated poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles as protein and peptide drugs (PPD) carriers. PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles or long-circulating nanoparticles, was synthesized with methoxypolyethyleneglycol (MePEG) and PLGA. The structure of PEG-PLGA was confirmed with (1)H NMR and Fourier transform infrared (FTIR) spectrum, and molecular weight was determined by gel permeation chromatography (GPC). Bovine serum albumin (BSA), chosen as model protein, was encapsulated within the stealth nanoparticles with the double emulsion method. The particles were characterized in terms of size, zeta potential and in vitro release of the protein. The biological fate of the BSA-loaded nanoparticles following intravenous administration was determined over 24 h in rats. The experimental results showed that PEG-PLGA could be obtained by ring-opening polymerization of lactide and glycolide in the presence of MePEG. (1)H NMR and FTIR spectrum were consistent with the structure of PEG-PLGA copolymer. Molecular weight determined by GPC was 50800. The stealth nanoparticles loading BSA could be prepared by the double emulsion technique. The entrapment efficiency was 48.6%, particle size about 200 nm and zeta potential -16.1 mV. BSA release from the stealth nanoparticles showed an initial burst release and then sustained release. PEG-PLGA nanoparticles could extend half-life of BSA from 13.6 min of loaded in PLGA nanoparticles to 4.5 h and obviously change the protein biodistribution in rats compared with that of PLGA nanoparticles. Thus, PEG-PLGA nanoparticles could be an effective carrier for PPD delivery.