The cefazolin-loaded chitosan–polyethylene oxide nanofibrous mats were fabricated. The fibers diameters were decreased by addition of fumed silica NPs to the mats. The cefazolin release from the optimized mat was sharply increased within first 6 h. The hydrophilicity/tensile strength of the mat with drug-loaded silica was appropriate. CS-PEO-F. silica-cefazolin nearly completely healed the wounded skins of Wistar rats.