Fluoroquinolone antibiotics with concentration-dependent killing effects and a well-established broad spectrum of activity are used commonly to treat infectious diseases caused by bacteria. However, frequent and excessive administration of these antibiotics is a serious problem, and leads to increased number of drug-resistant bacteria. Thus, there is an urgent need for novel fluoroquinolone antibiotic formulations that minimize the risk of resistance while maximizing their efficacy. In this study, we developed intramuscularly injectable polymeric microparticles (MPs) that encapsulated with marbofloxacin (MAR) and were composed of poly(d,l-lactide-co-glycolic acid) (PLGA) and poloxamer (POL). MAR-encapsulated MP (MAR-MP) had a spherical shape with particle size ranging from 80μm to 120μm. Drug loading efficiency varied from 55 to 85% (w/w) at increasing amount of hydrophilic agent, POL. Drug release from MAR-MP demonstrated a significant and sustained increase at increased ratios of POL to PLGA. These results indicate that MAR-MP is an improved drug delivery carrier for fluoroquinolone antibiotics, which can reduce the number of doses needed and sustain a high release rate of MAR for 2–3days. As a novel and highly effective drug delivery platform, MAR-MP has great potential for use in a broad range of applications for the treatment of various veterinary diseases.