The present research is aimed to explore permeation capabilities of a model drug diclofenac sodium from buffalo ghee as an oleaginous base. The four prototype compositions (F1 to F4) were prepared by using different proportions of buffalo ghee. The diffusion and permeability studies of the prepared compositions were studied by using Franz diffusion cell. The optimized composition (F4) was compared with marketed formulation. The study indicates that permeability and diffusion of the diclofenac sodium from the ghee base is dependent on the proportion of ghee. The diffusion and permeability of diclofenac sodium is highest at higher proportions as in F4.