Abstract: AimTo prepare glucagon-like peptide-1 (GLP-1) loaded long-acting injectable microspheres and to evaluate their In vitro release behavior as well as its pharmacodynamics. Methods GLP-1 loaded microspheres were prepared with poly(lactic-co-glycolic acid) (PLGA) as carrier materials by double emulsion (W/O/W) method. Physical and chemical characteristics of microspheres, such as mean diameter, morphology and drug loading were evaluated. The In vitro release behavior and its influencing factors were determined by HPLC, also the bioactivity of GLP-1 in the course of encapsulation process and In vitro release were evaluated by in vivo animal experiments. The effect of reducing plasma glucose about GLP-1 microspheres were evaluated on the diabetes mice. ResultsMicrospheres with good shape and dispersive quality were prepared. The drug entrapment efficiency was more than 80%. The accumulated release in one month is up to 85% and the release equation is in accord with zero-class release model. The bioactivity of GLP-1 was conserved with glutin as inner water phase, but in the course of In vitro release, the specific activity of GLP-1 in the microspheres decreased a little. GLP-1 microspheres can decrease the plasma glucose significantly and the effect can go on for one month. ConclusionGLP-1 can be encapsulated in injectable microspheres to yield one-month continuous release when using biodegradable polymers PLGA as carrier material, and this technique will have a favorable perspective in the near future.