This study was designed to evaluate the possible influences of betamethasone-17-valerate (BMV) on the gelation properties of sodium deoxycholate (Na-DOC), due to structural similarities as the monomer and the active agent. For this purpose gel formulations at two different concentrations, 0.05 and 0.1 % (w/w) were prepared and characterized by rheological and thermal analysis. The results indicated that the elastic moduli of the gels increased with increasing concentration of BMV in the system. This phenomenon was shown to be due to the modification of polymerization occurred by interactions between BMV and Na-DOC. The increment of BMV concentration in the formulation, caused a modification of the glass transition temperature (Tg) detected. Tg data pointed out a higher polymerization of Na-DOC with increasing amount of BMV. Transepidermal water loss measurements were also performed to evaluate possible skin irritation. It was observed that the degree of Na-DOC polymerization did not show any irritant effect on the skin.Overall, the results of this study clearly confirmed that incorporation of BMV into Na-DOC gel system produced a synergistic effect on product rheological characteristics, which would be beneficial for topical applications.