Abstract: AIMTo prepare bioadhesive microspheres of metronidazole (Metro) with prolonging resident time in the stomach and sustaining drug release. METHODSThe microspheres were prepared by a drying-in-liquid method. The appearance, particle size and drug release in vitro were examined. The factors influencing bioadhesive property and drug release, such as ethyl cellulose (EC) / carbopol 934P (CP) ratio, particle size and Metro content were investigated. RESULTSThe average diameter of the Metro-EC-CP microspheres was 559.9 μm. The release profiles of metronidazole were shown to fit to first-order equations well. With the increase of CP content in the Metro-EC-CP microspheres, the microspheres showed better mucoadhesion and faster drug release. The drug release rate decreased with the increase of particle size and the decrease of Metro content. CONCLUSIONThe Metro-EC-CP microspheres have a sound mucoadhsive property and sustained drug release when the ratio of EC and CP was 17∶3 and Metro content was 25%. The drug release was shown to last for 8 h in 0.1 mol·L^-1 hydrochloric acid.