Calcium oxalate stone disease is the most common human urinary stone disease in the Western Hemisphere. To understand different aspects of the disease, calcium oxalate urolithiasis in the rat is used as a model. Spontaneous calcium oxalate urolithiasis is very rare in rats. Thus the disease is experimentally induced and the rats are generally made hyperoxaluric either by administration of excess oxalate, exposure to the toxin ethylene glycol, or various nutritional manipulations. All the experimental models show renal injury associated with crystal deposition. Calcium oxalate crystals are in most cases intraluminal in renal tubules and often attached to the basal lamina of the denuded epithelium. Rat renal papillary tips and fornices appear to be the preferential sites for the deposition of large calcium oxalate calculi. Where urinary supersaturation of calcium oxalate has been studied the crystal forming rat urines are shown to have higher urinary supersaturation of calcium oxalate than their controls. Oxalate metabolism in the rat is nearly identical to that in humans. Thus, in a number of respects, experimental calcium oxalate urolithiasis in the rat is similar to calcium oxalate stone disease in man.