To gain a greater understanding of the mechanism of Cu metabolism in kidneys of rats, using autofluorescence of Cu-metallothioneins (Cu-MTs) we revealed the behavior of Cu-MT in the kidneys of rats administered Cu-MT. Yellow and orange fluorescent signals of Cu-MT were observed in the cortex. By microscopic studies, Cu-MT was dominant in the proximal convolute tubular cells of the cortex. A high concentration of Cu-MT presented in the lysosome-like organelles of the proximal convolute tubular adjacent to the glomeruli. During the time course after the injection, the orange signal in lysosome-like organelles gradually converted to a yellow signal, indicating that the Cu-MT was involved in a degradation process in lysosomes by oxidation, and the MT mRNA increased in the cortex, although the immunoreactivity of MT was almost constant in the same region. These results suggested that Cu bound to the injected MT was released in lysosomes and became a new inducer of MT biosynthesis in the cortex. In conclusion, the biosynthesis and degradation of Cu-MT occur repeatedly in the proximal convolute tubular cells.