Cubosomes are discrete, sub-micron, nanostructured particles of the bicontinuous cubic liquid crystalline phases.The aim of this work is to improve the bioavailability of tretinoin byformulating cubosomes. Cubosomal formulations were prepared according to aBox-behnkendesign. The selected variables were the amount of glyceryl monooleate, poloxamer 407 and amount of drug. In total fifteen batches were prepared. The prepared formulations were characterized for their drug content, particle size, zeta potential and in-vitro permeation study. The optimized formulation had a size of 128.3 nm, zeta potential (−29.2), and entrapment efficiency of 78.852% and showed a sustained release pattern over 12 hrs. Micrographs of the transmission electron microscope confirmed the cubic nanostructure of the optimized formulation. The optimized formulation was further transformed into gel utilizing carboxy methyl cellulose as gelling agent. The prepared gel was evaluated for appearance, pH, viscosity and in-vitro permeation study. The results depicted that the formulation showed uniform appearance, appropriate viscosity and about 91.948±0.011% drug was released in pH 6.8 Phosphate buffer at the end of 12 hrs in a sustained manner.