Mineral oil has been used to facilitate ureteral stone extraction and to treat selected patients with infected residual urine. The purpose of this study was to evaluate the effect of mineral oil on the urothelium. Twelve adult female farm pigs underwent bilateral ureteral catheter placement under general endotracheal anesthesia. Retrograde pyelograms were performed and the ureteral diameters measured. Using a randomization protocol, six animals underwent injection of 10 mL of normal saline into one ureteral catheter and 50 mL of normal saline instillation into the bladder. In the remaining six animals, 10 mL of mineral oil was injected into one ureteral catheter and 50 mL of mineral oil into the bladder. The instillation was maintained for 30 minutes, and then the catheters were removed. One week later, under general endotracheal anesthesia, cystoscopy and retrograde pyelography were performed to measure the diameter of the ureters, and the animals were euthanized. The bladder, ureters, and kidneys were harvested for macroscopic and histopathologic evaluation. There was no significant difference in the diameter of the ureters injected with normal saline, the uninjected ureters, or the mineral oil-injected ureters. The bladders, ureters, and kidneys were grossly normal in all animals. No significant histopathologic changes were noted in the ureteral or bladder urothelium or the renal parenchyma in the animals injected with mineral oil. In conclusion, the instillation of mineral oil within the urinary tract does not have any significant long-term functional or histopathologic effect on the urothelium.