The aim of this study was to evaluate the potential application of microemulsions as a transdermal drug delivery for naproxen (Np). The pseudo-ternary phase diagrams were developed for microemulsions composed of isopropyl myristate, Span 80, Labrafil M, Labrasol, and Cremophor EL, ethanol and isopropyl alcohol and 0.5N sodium hydroxide. The final concentration of Np in microemulsion systems was 10% (w/w). The microemulsions were characterised by conductivity, droplet size, viscosity and pH. Moreover, in vitro permeability studies were performed using diffusion cells from rat skin. The permeation rates of Np from microemulsions (M1(Np) and M2(Np)) were higher than the commercial (C) gel formulation. The paw oedema test was performed in rats to evaluate the anti-inflammatory activity of Np. The volume increase in paw oedema after 6hr was 0.71±0.46% with M2(Np), whereas M1(Np) and C exhibited 6.48±2.71% and 14.97±3.15% increases in oedema, respectively. Additionally, a significant analgesic effect was detected in the hot plate and tail-flick tests for all test microemulsion and C formulations when compared with the control. Histopathological examination of the treated skin was performed to investigate changes in skin morphology. In conclusion, the microemulsion formulations, especially the M2(Np) formulation, may be used as an effective alternative for the transdermal delivery of Np.