The lipophilicity (R(MW)) of betamethasone and its four related compounds: betamethasone-17,21-dipropionate, betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone disodium phosphate was determined by reversed phase HPTLC and various mobile phase systems (methanol-water, dioxane-water and acetonitrile-water). The chromatographic lipophilicity parameters obtained for all examined compounds using abovementioned mobile phases onto three chromatographic plates (RP-2F254, RP-8F254, RP-18WF254) were compared with the theoretical partition coefficients which have been calculated by different computing programs: AlogPs, AClogP, AlogP, MlogP, KOWWIN, xlogP2, xlogP3, logP(ChemDraw) as well as with logP measured by shake-flask method. The results of this work demonstrate that regardless of applied method the greatest similarity in lipophilic properties show betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone 17,21-dipropionate. The influence of solvent system as mobile phase on R(MW) values of examined compounds was observed. Among different mobile phases (organic modifier-water) proposed in this study, which allowed obtaining the reliable chromatographic lipophilicity parameters for all studied compounds is methanol-water mixture. The performance investigations showed that RP-HPTLC method has proved to be a rapid and cost effective analytical tool for describing the lipophilic properties of betamethasone and its related compounds.