To investigate fuel cladding chemical interaction in irradiated metallic nuclear fuels, diffusion couple experiments have been performed using prototypic metallic fuel alloys with additions of noble metal and lanthanide fission product components mated against stainless steel claddings. The developed interdiffusion zones have been characterized using SEM/EDS/WDS to determine the development of phases and the interdiffusion behavior of specific fuel, cladding, and fission product components. The formed diffusion structures have been compared to actual interaction zones that form in irradiated metallic SFR fuels. This paper discusses how the structures compare between the diffusion couple-generated interdiffusion zones and those that develop in irradiated metallic nuclear fuels. It was found that similarities exist between the phase development and interdiffusion behavior in the annealed diffusion couples and the irradiated fuels. Nd, Mo, and Ru, which were added to a fuel alloy to represent fission products that are present in irradiated metallic nuclear fuels, were found to exhibit interdiffusion behavior in annealed diffusion couples that was similar to what has been observed in actual irradiated metallic fuels. This was also true for the original fuel components U, Pu, and Zr, along with the cladding constituent Fe, Ni, and Cr.