Tramadol hydrochloride microspheres with cellulose acetate butyrate (CAB) polymer were prepared using water-in-oil emulsion non solvent evaporation technique, in an attempt to decrease the frequency of the dose from 4 to 6 times daily to twice daily. The Influence of different parameters such as drug to polymer ratio, concentration of span 80, stirring rate and viscosity of oil on the actual entrapment and yield percentage were studied. The actual entrapment and yield percentage were increased by increasing drug: polymer ratio, decreasing the stirring rate, decreasing span 80 concentration and decreasing the oil viscosity. The microsphere particle size was decreased by decreasing drug: polymer ratio, increasing the stirring rate, increasing span 80 concentration and increasing the oil viscosity. the effect of different parameters on the in-vitro release of tramadol hydrochloride from the prepared microspheres was also studied. The release rate was decreased by decreasing the drug: polymer ratio, decreasing span 80 concentration, decreasing stirring rate and decreasing oil viscosity. Analgesic activities of intact tramadol HCI alone and tramadol HCl microsphere were evaluated using hotplate method. The analgesic activities of the tested microspheres in-vivo were prolonged compared to that of the uncoated drug.