Background: Microspheres are the carrier linked drug delivery system in which particle size is ranges from 1-1000 μm range in diameter having a core of drug and entirely outer layers of polymer as coating material. The present study aimed at developing a microsphere of glimepiride using natural polymer for a longer duration of action. Material and methods: We formulated and evaluated of microspheres by natural polymer of Glimepiride and their Benefits of microsphere in drug delivery system. Microspheres of glimepiride was formulated using natural polymer chitosan. Antidiabetic effect of glimepiride microspheres and