In the present study clobetasol propionate (Cp) was loaded as solid lipid nanoparticles (SLN), incorporated it in suitable cream base and evaluated in vitro and its performance clinically against equivalent marketed formulation. Cp was incorporated into SLN by high-pressure homogenization technique and characterized for mean particle size, surface morphology and per cent drug entrapment. Drug permeation and skin uptake studies from Cp creams were carried out in a validated Franz static diffusion cell across human cadaver skin (HCS). Sixteen chronic eczema patients were enrolled in a controlled double blind clinical trial. Optimized Cp-SLN was smooth and spherical under scanning electron microscopy; with average particle size of 177 nm and per cent drug entrapment of 92.05%. In vitro permeation studies revealed lower mean flux value and higher skin uptake of Cp from Cp-SLN cream compared to marketed drug cream. Both formulations were found to be responsive to manifestations of chronic eczema, while Cp-SLN cream prepared in this investigation registered significant improvement in therapeutic response (1.9 fold; inflammation, 1.2 fold; itching) in terms of per cent reduction in degree of inflammation and itching against marketed cream. Further clinical trials are required to ascertain the efficiency of the present formulation.