[Abstract] Objective: To preparation exenatide loaded poly (lactic-co-glycolicacid) (PLGA) microspheres and to evaluate its release behavior in vitro. Methods: Exenatide PLGA microspheres were prepared by W/O/O method. The content and in vitro cumulative release was determined by a HPLC method, the physical and chemical characteristics of microspheres, including the mean diameter, morphology, drug entrapment efficiency and loading efficiency were evaluated. Results: The prepared microspheres were well-shaped, with mean diameter of (51.2±1.97)μm. The drug loading and encapsulation efficiency were (4.50±0.13)% and (88.6±0.73)%, respectively. The first day burst release was (13.19±1.39)%. The cumulative in vitro release was up to (88.6±0.73)% in 28 day. Conclusion: The exenatide can encapsulated in microspheres to yield a one-month continuous release using biodegradable polymers PLGA as the carrier material and the process is stable and reproducible.