Theophylline-loaded bovine serum albumin (BSA) microsphereswere prepared by an emulsion polymerization method usingglutaraldehyde as the crosslinking agent. The study was designedto evaluate the effects of different formulation parameters as BSAconcentration, surfactant concentration, hydrophilic lipophilicbalance (HLB), dispersion medium viscosity and glutaraldehydeconcentration on the extent of drug loading, size of microsphereand the in-vitro as well as the in-vivo release rates of theophyllinefrom such microspheres. Drug polymer ratios of 1:1, 1:2, 1:3, 1:4, 1:5 and 1:6 were investigated. Span 80 was used as a surfactant atdifferent concentrations. Moreover, Different span 80 / tween 80blend concentrations; 0.5, 1.0 and 2.0% w/v were used to study theeffect of HLB. Also different dispersion media; isooctane, lightparaffin oil, olive oil and Linseed oil were used for microspherespreparation. In addition, different glutaraldehyde concentrations;5, 10 and 25% v/v were used. It was found that all micro-sphereswere spherical with the mean particle size of 90-180 μm. Theresults revealed also that: as the concentration of BSA increases,the drug loading is increased. Increasing surfactant concentrationand viscosity of the dispersion medium has led to decrease theparticle size, while increasing glutaraldehyde concentration nearlyhad no effect. Furthermore, encapsulation efficiency was found tobe directly proprortional to albumin content, surfactantconcentration, viscosity of the dispersion medium andglutaraldehyde concentration. Drug release from the preparedmicrospheres displayed a biphasic pattern characterized by aninitial burst, followed by a slower release period, which may beattributed to the presence of theophylline material near to or ontothe microspheres surfaces. The bioavailability of theophylline fromthe prepared microspheres was evaluated in rabbits. The preparedmicrospheres were found to control theophylline release even up to10 hrs. The peak serum concentrations of such microspheres werewithin the therapeutic level. The results indicate also that theprevioiusly mentioned formulation parameters have a prnouncedimpact to control the release of the entrapped drug.