Reported in this study is the successful incorporation of a hydrophilic antibiotic drug, tetracycline hydrochloride (TCH), into electrospun PEG-PLA nartofibrous membrane without loss of its bioactivity. Degradation behavior of the copolymer was studied in vitro. Release behavior of TCH from the electrospun membrane and antimicrobial effects of the TCH-loaded membrane against Staphylococcus aureus culture were investigated. The medicated nanofibrous membrane demonstrated sustained release of TCH over 6 days and was found to be effective in inhibiting growth of S. aureus. In addition, increasing the antibiotic drug content in the electrospun membranes was found to enhance the anti-bacterial effectiveness of the medicated fiber mats. And the combination of mechanical barriers provided by the electrospun biodegradable nanofibrous membranes and their capability of local sustained delivery of antibiotics made these membranes more useful in biomedical applications, particularly as new wound dressings for ulcers caused by diabetes or other diseases, and to provide a better means of treatment for these malignant wounds and ulcers. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 118: 588-595, 2010