Abstract: Objective To prepare piroxicam nano cream and investigate its transdermal absorbability in vitro. Methods The nano cream was prepared by using oleic acid, glycerol monostearate, stearic acid as the oil phase, Cremophor EL as the surfactant and propylene glycol as the co-surfactant ., and its appearance, mobile phase, particle size distribution and other physical and chemical properties were evaluated. The transdermal characteristics were evaluated by using abdominal skin of mice on Franz diffusion cells, and the drug concentration was measured by UV detector. Results The optimal prescription of nano cream in the experiment is 2.8% oleic acid, 4.6% glycerol monostearate, 2.2% stearic acid, 8.4% propylene glycol, 33.6% polyoxyethylene castor oil, 48.4% water . The particle size of nano-cream after water-dispersion was 216.6 ± 10.2 nm . Transmission electron microscopy showed uniform distribution of spherical droplets structure s. The cumulative transdermal quantities of piroxicam nano cream in 72h was significantly higher than the piroxicam solution . Q72 and Js were 2.1 times and 2.3 times that of piroxicam, respectively . Conclusion The nano cream prepared by this method has strong transdermal ability and good fluidity, and is expected to be a new transdermal preparation for piroxicam