This study is focused on the uptake of PLGA particles with different coatings and its influences on the functions and toxicity of human endothelial cells. The PLGA particles coated with polyethyleneimine (PEI) or bovine serum albumin (BSA) were prepared via a one-step emulsion method, which had a similar diameter of similar to 420 nm in water and similar to 170 nm in a dry state but oppositely charged surfaces. Both types of the particles were readily internalized into cells within a short time regardless of their surface chemistry. Uptake of the positively charged particles caused apparently a decrease in cell viability, but did not significantly influence mitochondrial membrane potential and activity of caspase-3. The cell adhesion and migration were significantly affected, especially after uptake of the PLGA-PEI particles. The secretion levels of von Willebrand factor (vWF) and 6-k-PGF(1 alpha) were not significantly influenced regardless of the surface coating.