Solid bonding diffusion couples of U-Mo/Nb were prepared by coating and hot rolling. The diffusion couples were heat-treated at 760 oC and 790 oC for different time. The distribution of the main diffusion elements in linear dimension was measured by Energy Dispersive Spectrometer (EDS). The model of diffusion in semi-infinite media was established according to the experiment’s initial boundary conditions. Error function solutions of the diffusion equation were also presented. The diffusion coefficient of uranium diffused in Nb base metal was calculated with the experimental data. The calculation result is considered to be correct by analyzing the method of experiment