The equilibrium in the isotope exchange reaction between U-235-enriched UF5 nanoparticles and natural UF6 gas was experimentally investigated. From the relationship between the isotopic fraction of UF6 gas at equilibrium and the specific surface area of the UF, nanoparticles, it was experimentally demonstrated for the first time that all UF5 molecules on the outermost layer of the particles participated in the reaction until the isotopic fraction of UF5 on the outermost layer became equal to that of the UF6 gas. A fast rate process during the early period of the reaction and a subsequent slow rate process were quantitatively observed. These facts contradict the previously reported assumption not supported by experimental evidence that the UF5-molecules in the underlying layer of the particle participate in the reaction. A new model based on our experimental findings was proposed. Our model suggests that there are two kinds of molecules on the outermost layer with different reactivities and all UF5 molecules on the outermost layer contribute to the reaction. The rate equations were derived from the proposed model and analytically solved. The time dependency of the isotopic fraction of the UF6 gas and UF5 particles was expressed by three kinetic parameters such as the rate constant of the high reactivity molecule, k(s), the rate constant of the low reactivity molecule, kj, and the fraction of high reactivity molecules on the outermost layer, xi. Our model reproduced well all the experimental data determined in the present study with k(s) =5.5x10(-20)cm(3)/(s molecules), k(s)'=4.5x10(-22) cm(3)/(s molecules), and xi=0.078.