question: BACKGROUND The research of extracellular matrix stent (ECM) has made some progress in the repair of urethra and bladder defects. OBJECTIVES To observe the effects of highly bioactive ECM scaffold on the regeneration and repair of defects in long-segment ureteral replacement. MATERIAL AND METHODS An animal model of long-segment ureteral defect was established and four-layer tubular highly bioactive ECM materials were prepared. After the ureteral defect was repaired through surgery, the rabbits in the negative control group were administered a non-bioactive stent, and rabbits in the observation group were treated with an ECM stent. RESULTS Comparison of macro-indicators: The negative control group had a higher infection rate, a lower survival rate and more complications than the observation group (p < 0.05). The frequency of ureteral peristalsis in the negative control group was lower than in the observation group. In addition, the rate of urinary dysfunction was higher, and the ratio of ureteral diameter was lower in the negative control group than in the observation group (all p < 0.05). Comparison of histopathology: Three months after the operation, the vascular, smooth muscle and mucous membrane of the ureter in the observation group regenerated to close to normal ureteral tissue. There was no significant difference between the ureter regeneration in the repair area and the normal ureter tissue in the observation group 3 months after the operation. The number of regenerated muscle fibers in the observation group was significantly higher than that of the negative control group. Compared with the negative control group, the fibrous capsule was thicker, the percentages of CD31, CD3, CD68, CD80+, and CD163+ were higher, the scope of new smooth muscle fiber was expanded, fusion with the host muscle fibers was higher, and the neuromuscular junction (NMJ) structure was stronger in the observation group (all p < 0.05). CONCLUSIONS A highly bioactive ECM stent can better regenerate the local anatomical structure and physiological function.