The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential ofw/o microemulsion (M) and gel (G) bases for diclofenac sodium (DS). The effect of dimethylsulfoxide (DMSO) as a penetration enhancer was also examined when it was added to the Mformulation. To study the in vitro potential of these formulations, permeation studies wereperformed with Franz diffusion cells using excised dorsal rat skin. To investigate their in vivoperfoniranc e, a car-rageenan - induced rat paw edema model was used. The commercial formulationof DS (C) was used as a reference formulation. The results of the in vitro permeation studies andthe paw edema tests were analyzed by repeated - measures analysis of variance. The in vitropermeation studies found that M was superior to G and C and that adding DMSO to M increasedpermeation rate. The permeability coefficient (Kp) of DS from M and M + DMSO were higher(Kp :4.9 X 10 -3 +3.6 X l0 -4 cm lhand 5.3 X 10 -3 + l.2X 10 -3 cm / h, respectively) than the($p) of nS from C (Kp: 2.7 xl0-3 +7.3 X 10 -4 cm /h) and G (Kp:4.5 X i0 -3 x+.s X 10 -scm / h). In the paw edema test, M showed the best permeation and effectiveness, and M + DMSOhad nearly the same effect as M. The in vitro and in vivo studies showed that M could be a new,altemative dosage form for effective therapy.