Objectives: The aim of this study was to determine the toxicity of calcium oxalate at different periods of exposure to epithelial cells of proximal renal cell types MDCK type I. Furthermore, to evaluate the effectiveness of caffeine in the formation of calcium oxide crystallization in the urolithiasis cellular model and measure the glutathione concentration in epithelial cells of proximal MDCK type I cell carcinoma tubes after treatment with calcium oxalate and caffeine. Study design: Laboratory research study. Materials and methods: Chemicals used included calcium oxalate (Sigma - Aldrich) and caffeine (Sigma). The cell culture used in the study was Madin - Darby's canine kidney cells subtype I (MDCK type I). Cells incubated to full confluence were treated with calcium oxalate and caffeine at appropriate concentrations and incubated at 37°C at 5% CO2 and light microscopy followed the formation of crystallization after 1 hour, 3 hours, and after 24 hours. The concentration of total glutathione (tGSH) was measured by spectrophotometry using a commercially available kit (Glutathione Assay Kit, Sigma - Aldrich, Saint Louis, MO, USA), according to the manufacturer’s protocol. Cell survival was determined by the exclusive Trypan Blue (Sigma - Aldrich, St. Louis, USA) suspension dye using Neubauer's hemocytometer under a light microscope. Results: After incubating cells with calcium oxalate crystals at various caffeine concentrations, caffeine has been shown to cause a significant reduction in the number of crystalline calcium oxalate and significantly increase cell viability proportionally to increased concentrations. Furthermore, measured total glutathione concentrations showed a decrease in the oxidative load of the treated cells with caffeine and calcium oxalate compared to the cells treated only with calcium oxalate. Conclusion: The protective effect of caffeine on MDCK type I cells has been shown to be toxic to the action of calcium oxalate crystals. Caffeine represents potential therapy in the treatment of urolithiasis, i.e. a preventative substance for the production of kidney stones. Also, the results suggest that caffeine is a potential antioxidant in the prevention of oxidative cell damage.