A family of newly synthesized monomethoxy (polyethylene glycol)-poly (D,L-lactic glycolic acid)monomethoxy(polyethylene glycol) (MeO-PEG-poly (D,L-lactic-co-glycolic acid)-PEG-OMe, PELGE) biodegradable polymers are candidates for intravenous nanoparticle drug, because of their merits of biocompatibility and blood compatibility, and their capability of escaping from the endothelium system (RES) and adsorbing proteins. In the current research, relationships between composition, cytotoxicity, and hemocompatibility of a series of blank PELGE nanoparticles were investigated. Cytotoxicity on Chang cell lines was investigated using the methyl thiazolyl tetrazolium (MTT) assay. Human and rabbit blood were used in studies of red blood cell hemolysis, whole blood clotting time, plasma recalcification profiles, and red blood cell form and appearance in whole blood. The results that the molecular weight of PEG used in the synthesis of polymers influenced their characteristics. Generally, as the molecular weight of PEG increased, increased cytotoxicity and hemocompatibility were observed. The RGR (relative growth rate) of PELGE nanoparticles synthesized with PEG 550 was above 70%, while that of PELGE nanoparticles synthesized with PEG 750 and PEG 2000 was in the range of 55-105% and 36-87%, respectively. For PELGE nanoparticles synthesized with PEG 550, most hemolysis values were in the range of 13%, while for PELGE nanoparticles synthesized with PEG 750 and PEG 2000 hemolysis values were 1-2%, and below 2%, respectively. None of the nanoparticles Caused changes in red blood cell form or appearance. Based on the results, 12 kinds of PELGE were chosen for further studies. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 2933-2944, 2009