5-Fluorouracil-poly(L-lactide) (5-Fu-PLLA) microparticles have been prepared by an SEDS process. First, the 5-Fu is successfully micronized and is then used to produce the 5-Fu-PLLA microparticles. The 5-Fu-PLLA microparticles synthesized by the SEDS process exhibit a rather spherical shape and a narrow particle size distribution, where it ranges from 615 to 1990 nm, with a mean particle size of 980 nm. The dichloromethane residue in the 5-Fu-PLLA microparticles without any further treatment is 46 ppm. The average drug load and encapsulation efficiency of the 5-Fu-PLLA microparticles are 3.05 and 17.8%, respectively. The rate of drug release from the 5-Fu-PLLA microparticles shows mainly first-order kinetics.