Background Intestinal ischemia can quickly escalate to bowel necrosis and perforation. Transplantation of stem cells presents a novel treatment modality for this problem. We hypothesized that: (1) Human adipose derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared to differentiated cellular controls following ischemic intestinal injury, (2) improved outcomes with hASC therapy would be associated with preservation of intestinal histological and tight junction architecture, and lower levels of systemic inflammation following intestinal injury. Methods hASCs and keratinocytes (differentiated cellular control) were cultured on polystyrene flasks at 37C in 5% CO2 in air. Adult male C57Bl6J mice were anesthetized and a midline laparotomy performed. The intestines were eviscerated, the small bowel mesenteric root identified, and intestinal ischemia was established by temporarily occluding the superior mesenteric artery for 60 minutes with a non-crushing vascular clamp. Following ischemia, the clamp was removed and the intestines were returned to the abdominal cavity. Prior to abdominal closure, two million hASCs or keratinocytes in 250 uL of PBS (carrier for cells and control solution) were infused into the peritoneum. Animals were allowed to recover for 12 or 24 hours (perfusion, histology, cytokine, and immunofluoresence studies), or 7 days (survival studies). Intestinal perfusion was assessed by laser Doppler imaging. Intestinal tissue segments were stained with H&E, as well as antibodies for the tight junction protein claudin-1. Separate aliquots of intestine, liver and lung tissue were homogenized and assessed for inflammatory cytokines via multiplex beaded assay. Results Animals administered hASCs following intestinal ischemia and reperfusion injury (I/R) had significantly greater 7 day survival and better post-ischemic recovery of mesenteric perfusion compared to vehicle or keratinocyte therapy. hASCs also abated intestinal mucosal destruction, facilitated preservation of intestinal tight junctions, and decreased the systemic inflammatory response to injury. Conclusion Human adipose derived stromal cells improved survival and mesenteric perfusion and attenuated the mucosal damage associated with intestinal ischemia and reperfusion injury. hASCs should be considered as a plausible cell source for novel cellular treatment plans following intestinal ischemia.