In this study, a novel poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) (P(HB-HO)) microparticle with an encapsulated antibiotic (azithromycin, AZI) was prepared by the electrospinning method. The resulting microparticles were evaluated for surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug-release and degradation. The in vitro cytotoxicity and in vivo pharmacokinetics were also studied. The sizes of microparticles showed a narrow monodisperse size distribution approximately from 3 to 30 mm. In vitro release experiments exhibited sustained release behavior. The results of in vitro degradation tests demonstrated that the mass loss of the P(HB-HO) microparticles was 9.6% and the morphology varied greatly within 24 weeks. P(HB-HO) showed no cytotoxicity to fibroblast when incubated with blank P(HB-HO) microparticles during the tests. The in vivo pharmacokinetic study demonstrated that the microparticles exhibited longer circulation properties than free AZI. It is suggested that novel AZI-loaded P(HB-HO) microparticles can be utilized as a biodegradable and biocompatible drug delivery system.