Background and Purpose: Endopyelotomy is the preferred treatment for ureteropelvic junction (UPJ) obstruction because of its short operating time, limited morbidity, fast recovery, and reasonable efficacy. We used tissue and immunohistochemistry staining and electron microscopy to look at the muscle regeneration following an endopyelotomy incision in a porcine model. Materials and Methods: Bilateral electrosurgical endopyelotomy was performed in six domestic pigs with placement of 7F 20-cm Percuflex® double-J stents for up to 4 weeks, and urinary tracts were harvested at 3 or 5 months. Specimen evaluation included tissue staining with hematoxylin-eosin, Masson's trichrome, and Verhoeff's iodine and Van Gieson solution; histochemical staining for smooth-muscle actin, desmin and myosin staining, and electron microscopy. Each specimen was assigned a "healing" score of 0 (normal) 1 (slight changes), 2 (mild changes), or 3 (severe changes). The fibrosis score was based on six factors: muscle layer fibrosis, lamina propria fibrosis, amount of granulation tissue present, new deposits of collagen, fibrosis in the periureteral fat, and presence of myofibroblasts. The muscles were characterized with immunohistochemistry and electron microscopy. Results: At both 3 and 5 months, the urothelium was healed, and the lamina propria was healed with focal loss. By 3 months, smooth-muscle bundles bridged the defect, and by 5 months, the whole defect was covered. Smooth muscle cells were evident by electron microscopy by 3 months, and actin and myosin could be detected by immunohistochemistry. Desmin-positive cells accounted for 50% of the population at 3 months and 40% at 5 months. The regenerated smooth-muscle bundles were oriented in different directions and intermingled with fibrous tissue. They could be distinguished easily from normal ureter under the microscope. Conclusion: Verifiable, functional smooth-muscle bundles bridge the endopyelotomy defect by 3 months, as confirmed by immunohistochemistry staining and electron microscopy.