To refine the assay for degradation/dissolution COM crystals examination and determine the degradation/dissolution mechanisms of calcium oxalate monohydrate (COM) crystals by renal tubular epithelial cells. Novel fluorescent-label COM crystals were successfully produced and treated with MDCK cells. Consequently, the degradation/dissolution internalized fluorescence COM crystals after 24-h were studied by crystal size and intracellular and extracellular fluorescent intensity. Internalized COM crystals were decreased their size and fluorescent intensity in contrast to extracellular fluorescent intensity by time dependent manner after 24-48h incubation. Localization of intracellular COM crystals was analyzed by immunofluorescence with early (Rab5) and late (Rab7) endosome marker. Accordingly, Rab5 and Rab7 were found in enlarge early endosomes with contain COM or degraded COM crystals. Therefore, Rab5 regulated enlarge endosome and endosome fusion might be the main mechanism of degradation/ dissolution of COM crystals by renal tubular epithelial cells. Further studies in the enlarge endosome molecular mechanism will lead to increase understanding of these mechanism.