Abstract Aim Anastomotic leak is a detrimental complication following bowel surgery leading to prolonged hospital stay, increased healthcare costs and significant increase in morbidity and mortality. The aim of this study is to investigate the effect of adipose derived mesenchymal stem cells (MSCs) mixed with platelet rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment . Method Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP + MSCs. All groups underwent laparotomy, segmental colectomy and anastomosis in situ. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. Results Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p=0.0151 and p=0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP + MSCs group, but not statistically significant. Neoangiogenesis (p=0.0073) and anastomotic area epithelialization (p=0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Conclusions The synergic effect of the PRP and MSCs is shown to significantly improve healing in bowel anastomoses even on a background of inflammation. These results give hope for primary anastomosis and potentially avoiding stoma and its complications, especially in immunocompromised or malnourished patients undergoing bowel resection. Clinical studies should follow in order to support the clinical application of PRP and MSCs combination in gastrointestinal anastomoses.