A series of polyethylene glycol derivates was synthesized by the reaction of α-chloroacetyl isocyanate with polyethylene glycol. Owing to the good reactive activity of α-chlorin in terminal it can react with 5-fluorouracil, the prodrug could be obtained. The prodrug was characterized by FT-IR, 1H-NMR and UV spectroscopy and confirmed that the 5-fluorouracil unit was successfully connected to polyethylene glycol terminal. The maxmium loading content of prodrug was 22.6% measured by UV and it showed enhanced water solubility and longer duration of activity due to slow release compared with 5-fluorouracil. The prodrugs could release 5-fluorouracil or its derivatives in different pH solution. When the moleculare weight reaches 2000, it has the fastest hydrolyzation speed, the maximum drug release percentage was 71.5% in 20h.