Abstract: Medicated ultrafine fiber mats were prepared using electrospinning with polyacrylonitrile (PAN) as matrix and acyclovir as model drug. The mats were characterized by scanning electron microscope (SEM), infrared spectroscopy (IR) and in vitro dissolution tests. SEM images envisaged that the diameters of fibers increased slightly with the increase of acyclovir contents in the fibers, and that fine drug particles were observed clearly on the fiber surface when the ratio in weight of acyclovir to PAN was 20 to 100. IR spectra results showed that that acyclovir had fine compatibility with PAN. In vitro dissolution tests indicated that the initial burst effects were obvious, and even more manifest when the content of acyclovir in the fibers increased, and meanwhile the total drug release percentage increased. All the ultrafine fiber mats were able to control the release of over 60% of acyclovir sustainedly via diffusion mechanism. Electrospun medicated fiber mats may offer novel strategies for the research and development of transdermal drug delivery systems or topical drug delivery systems.