Objective: The objective of this study was to compare and evaluate in vitro ex vivo transdermal potential of the diclofenac sodium (DS) gel by different permeation enhancers using Franz-type diffusion cells. Methods: DS gel was prepared with carbapol, DMSO, oleic acid (OA), and menthol with 1% weight/weight concentration each as the penetration enhancer. The in vitro, ex vivo permeability were determined using cellophane membrane and abdominal rat skin. Steady-state flux, permeability coefficient (kp), diffusion coefficient, and lag time were calculated Results: Menthol, at the concentration of 1% weight/weight, shows maximum kp, diffusion coefficient permeation enhancement effect with an enhancement ratio 40%, as compared to DMSO and OA. Conclusion: This finding predicts that DS gel 1% weight/weight containing menthol 1% weight/weight can possibly deliver therapeutically relevant dose of DS.