Epinephrine is an important hormone used in most plastic surgery and local anesthetic administration for the constriction of the blood vessels. In efforts to fabricate controlled delivery system of this vasoconstriction agent, epinephrine was encapsulated to alginate based microspheres. Twenty nine different formulation types were designed by varying the variables such as concentrations of alginate, crosslinking agent, and coating material. The differences in the formulation variables resulted in the morphology of microspheres, loading efficiency and release rate of epinephrine. Among 29 formulas, five were selected for in vivo study using rats. The epinephrine microspheres prolonged the sciatic nerve blockade for 7-11 hours when used with lidocaine in rats. The findings in the present study indicated that we can control the fabrication of alginate microspheres which could release epinephrine at various rates.