U-Mo alloys are being developed as low enrichment uranium fuels under the Reduced Enrichment for Research and Test Reactor Program. Previous investigation has shown that the interdiffusion between U and Mo in γ(bcc)-U solid solution is very slow. This investigation explored interdiffusional behavior, especially in regions with high Mo concentration, and the potential application of Mo as a barrier material to reduce the interaction between U-Mo fuel and Al alloys matrix. Solid-to-solid U-10wt.%Mo versus Mo diffusion couples were assembled and annealed at 600, 700, 800, 900 and 1000 °C for 960, 720, 480, 240, 96 h, respectively. The interdiffusion microstructures and concentration profiles were examined via scanning electron microscopy and electron probe microanalysis, respectively. As the Mo concentration increased from 22 to 32 at.%, the interdiffusion coefficient decreased while the activation energy increased. The growth rate constant of the interdiffusion zone between U-10wt.%Mo versus Mo was also determined and compared to be 104-105 times lower than those of U-10wt.%Mo versus Al and U-10wt.%Mo versus Al-Si systems. Other desirable physical properties of Mo as a barrier material, such as neutron adsorption rate, melting point and thermal conductivity, are also highlighted.