A series of novel polyethylene glycol derivates was synthesized by esterification of chloroacetic acid with polyethylene glycol.The PEG-5-FU conjugates were characterized by FT-IR, 1H-NMR and UV spectroscopy. The result showed that 5-FU was successfully connected to the ends of PEG ester. Drug content of PEG2000-5-FU conjugate achieved 17.4%. As the molecular weight of PEG increased, the water solubility of prodrugs improved. When the molecular weight of PEG reached 2000, the conjugate had the best water solubility and the highest drug release rate.