This study investigated whether the surface quantities of the additives and protein delivery characteristics for protein-loaded PLGA 85 (85: 15), PLGA75 (75: 25) and PLGA 50 (50: 50) microspheres with hydrophobic additives, phosphatidylcholine (PC) as a model, are affected by the different ratios of lactide and glycolide in PLGA polymers. By applying phospholipids analysis, surface PC quantities of the microspheres are 2.1 +/- 1.2, 1.2 +/- 0.3 and 1.0 +/- 0.7 mu g (n = 3) per mg of PLGA 85, PLGA 75 and PLGA 50 microspheres with PC addition, respectively, that are affected by the ratio of lactide and glycolide in PLGA. The addition of PC causes the decreased encapsulation efficiency (E.E.) of albumin of the microspheres and the decreased percentages of E.E. are negative correspondent to ratio of lactide and glycolide in PLGA (e.g. -13.5, -20.2 and -24.5% for PLGA 85, PLGA 75 and PLGA 50, respectively) compared with those without addition. The cumulative releases of albumin were influenced by the ratio of lactide and glycolide in PLGA for both PC addition and non-addition microspheres. Moreover, the additions of PC reduce the initial burst and cumulative releases of albumin of the microspheres compared with those of non-added ones. Further investigation suggests that resistant water uptake of PC added microspheres may play a role on affecting those reduced protein release behaviours. In conclusion, the different ratios of lactide and glycolide in PLGA affect the surface quantities of PC, E.E. and cumulative release profiles of albumin for the PLGA microspheres with PC addition. The results of the study may help the better practical applications for protein delivery of the microspheres with hydrophobic additives.