Objective To study the effect and histocompatibility of urethral extracellular matrix in repair of traumatic urethra defects in rabbits. Methods Model of traumatic urethral defects was made by resecting 1.0-1.5 cm segment of the urethra in 20 rabbits. Then, the defects were repaired by a tube of extracellular matrix of the same length. The dynamic changes of CD4+, CD8+ T cell and CD4+/CD8+ in peripheral blood were detected by flow cytometry at 1,2, 3 and 4 weeks after operation. In the meantime, the immunity response of rabbits was evaluated by lymphocyte transformation test. The repaired segments stained with hematoxylin-eosin (HE) and Van Giesen were studied by histologic and pathologic observations at 10 days, 3, 6 and 24 weeks postoperatively. The urodynamics, urethroscopy and urethrography were performed at 24 weeks postoperatively. Results There was no significant difference in aspects of stimulative index of lymphocyte transformation, T lymphocyte subsets CD4+, CD8+ T cell and CD4+/CD8+ between experimental group and negative control group. Urothelium covered the whole surface of the matrix tube three weeks after operation. The smooth muscle cells increased nearly to normal urethral wall at 24 weeks. Urethrosoopy and urethrography showed glossy matrix tube. There was no statistical difference upon urodynamies between experimental group and control group. Conclusion The urethral extracellular matrix has good histocompatibility and may be a safe and effective material for repairing urethra defects.