Small intestinal submucosa (SIS) is an unusual tissue that promotes constructive tissue remodeling when applied as a xenogeneic material. The aim of our experimental study was to assess its effectiveness in intestinal regeneration. Twenty white New Zealand rabbits were anesthetized and underwent celiotomy. A 6-cm antimesenteric incision was created at the jejunal segment. An elliptical SIS graft measuring 6 cm long and 2 cm wide was sutured to the jejunal defect as a patch graft. Thirteen living rabbits were divided into groups of three and the grafts were harvested at postoperative weeks 2, 4, and 6. The obtained specimens were evaluated for gross and histologic appearance. In morphometric examination, in the 2, 4, and 6 weeks groups, the diameters of grafted intestines were larger than preoperatively by 50%, 25%, and 25% respectively; also the grafts had contracted to 0%, 25%, and 50% of their original sizes respectively. At the end of 2 weeks, the grafts were intact without evidence of epithelial regeneration. By 4 weeks, intestinal tissue regeneration was started, and epithelial coverage of the grafts was detected. The grafts were covered with a complete intestinal mucosa at 6 weeks. Remarkable regeneration marked fibroplasia, angiogenesis, and mild mononuclear cell infiltration had also occurred throughout the grafts at 6 weeks. Porcine SIS appeared an effective biodegradable scaffold, facilitating regeneration of intestinal tissue. These results suggest that SIS may be useful to increase the mucosal surface of intestine and may provide a new substance for short gut syndrome in the future.