Introduction: Wound healing complications are frequently observed in transplant patients under a immunosuppressive regimen with sirolimus and administration of mycophenolate mofetil has been demonstrated to impair healing of colonic anastomoses. Intraperitoneal hyperthermic chemoperfusion (IHCP) reduces progression of peritoneal carcinomatosis following oncological surgery but leads to an increased leakage rate of intestinal anastomoses. Administration of Insulin-like growth factor-I (IGF-I) and truncated keratinocyte growth factor (tKGF) improves healing of bowel anastomosis in rats (Br J Surg 2001;88:90). The aim of the present study was to evaluate whether IGF-I or tKGF may prevent anastomotic healing problems in pigs undergoing IHCP with/without sirolimus administration. Materials/Methods: 24 pigs were divided into 4 groups (A-D). Sirolimus was administered orally during 7 days prior to surgery (15mg/d) and after surgery (5mg/d) until sacrifice on postoperative day 4. Laparatomy and division of bowel was performed followed by intramucosal injections of IGF-I (A: 5mg), tKGF (B: 5mg), vehicle IGF-I (C) or vehicle tKGF (D) into the bowel dissection margins. Suturing bowel anastomosis was followed by IHPC with a Mitomycin-C solution (4 Liters; 10mg/L,41.5°C, 1h). 18 additional control pigs (n=6 group E-G) received either +sirolimus, +NaCl-injection, +isothermic NaCl-perfusion (E), or –sirolismus, +NaCl-injection, +IHPC (F) or –sirolimus, +NaCl-injection, +isothermic NaCl-perfusion (G). Mechanical stability of anastomosis was evaluated by measuring the bursting pressure (BP). Results: In all experimental and control groups BP's [mmHg; mean ± SEM] were statistically not different: Group A: 95±61 in the small intestine vs. 112±13 in the colon, B: 100±34 vs. 90±26, C: 132±48 vs. 96±10 and D: 160±36 vs. 104±14. BP's of anastomoses were comparable to those observed in the additional control groups (E-G): E: 135±50 vs. 90±15, F: 146±28 vs. 90±35 and G: 130±40 vs. 98±18. Conclusions: Administration of sirolimus with/without IHPC does not impair mechanical stability of bowel anastomoses in healthy pigs. Since bursting pressures did not differ between experimental and control groups our experiments were unable to demonstrate a beneficial effect of locally applied IGF-I and tKGF. However, immunosuppression with sirolimus, that is often associated with wound healing complications in humans, does not impair mechanical stability of intestinal anastomosis in pigs.