The aim of this study was to optimize the chitosan/polycaprolactone (CS/PCL) electrospun nanofibrous membrane with random/aligned fiber structures to provide a controlled release of ciprofloxacin (Cip) and guide skin fibroblasts arrangement. A series of Cip-encapsulated CS/PCL electrospun membranes were prepared by coaxial-electrospinning. The existence of Cip in core-shell structured fibers was confirmed by using SEM, TEM and FTIR characterizations. The in vitro drug-release profiles suggested that the Cip presented a sustained release for 15days. Simultaneously, cyto-compatibility of the membranes decreased with the increasing amount of Cip from 2.0% to 5.0%. In particular, aligned CS/PCL membrane loading with 2.0% Cip exhibited a good balanced ability between cell proliferation and antibacterial effect (>99% against Escherichia coli and Staphylococcus aureus), which significantly accelerated the wound healing process in vivo. These results suggested that the aligned CS/PCL membrane loading with 2.0% Cip exhibited great antibacterial property and biocompatibility, which possess promising applications potential for wound healing.