OBJECTIVE： To screen the formulation of 5-fluorouracil （5-FU） polylactic acid （PLA） sustained-release discs （5-FU-PLA-DS）， and study its in vitro drug-release mechanism. METHODS： UV spectrophotometry was used to determine the 5-FU content in the release medium. Using simulate body fluid as release medium， in vitro drug-release test was conducted under 37 ℃ water bath. Using PLA with molecular weight of 3 000， 6 000， 10 000， 15 000， 20 000， 15 species of round 5-FU-PLA-DS with drug containing of 1.5， 2.5， 3.0 mg/piece and 3.0 mm in diameter and 1.0 mm in thickness were prepared. Using effective concentration sustained release time and cumulative release rate as indexes， the optimal formulation was screened. The form of 5-FU-PLA-DS was observed by scanning electron microscopy after release， and its release mechanism was evaluated. RESULTS： In the optimal formulation， the PLA molecular weight was 20 000 and drug containing was 3.0 mg/piece. The prepared 5-FU-PLA-DS can release for 119 d， with cumulative release degree of 100.63％ and effective concentration sustained for 91 d. Scanning electron microscopy showed that the microspheres at the surface were degraded to the release medium first， and then the microspheres of inner layer exposed and release drug gradually after PLA degraded. The main mechanism of drug-release was melting and diffusion. CONCLUSIONS： 5-FU-PLA-DS is successfully prepared， with long release time in effective concentration， can be degraded step by step from outside to inside and achieve non-synchronous drug-release of microspheres at different layers.