The purpose of this investigation was to prepare and characterize acyclovir loaded floating microspheres by emulsification solvent evaporation method. Piperine was added to investigate its effect on acyclovir bioavailability. The microspheres were characterized for size, shape, entrapment efficiency, in vitro drug release, and in vivo pharmacokinetic parameters. The morphological characterization of microspheres was done using a scanning electron microscope. The microspheres were spherical and had particle size in the range of 400 to 525 μm.