Abstract: AIMTo prepare sustained release fluorouracil microspheres for intratumor injection increased antitumor effect. METHODSAn O/W emulsion-solvent evaporation method was used to prepare fluorouracil sustained release microspheres. The characterization, drug release in vitro and antitumor effect of fluorouracil sustained release microspheres for intratumor injection on solid tumor such as Lewis lung cancer were investigated. RESULTSThe drug loading was (10.30±0.20)%, and the encapsulation efficiency was (68.3±1.5)%. The appearance of fluorouracil sustained release microspheres was smooth and spherical. Fluorouracil was physically incorporated with little burst effect. The T_1/2 in vitro release from the microspheres was 168 times longer than fluorouracil, with drug diffusion and polymeric erosion controlled mechanism. The inhibition rate of fluorouracil microspheres was 60.6% and the side effect was reduced. CONCLUSIONThe prepared fluorouracil sustained release microspheres was shown to be satisfactorily effective to lung cancer. The intratumor injection seems to be a potential chemotherapeutic approach.