Incisional hernias are a frequent complication of upper abdominal wall interventions, especially in patients undergoing liver transplantation with subsequent immunosuppressive therapy. Therefore, we analyzed in this study the manner in which the incorporation of a surgical mesh for hernia repair is affected by the immunosuppressant drugs rapamycin and cyclosporine A (CsA). For this purpose, Ultrapro meshes were implanted into the dorsal skinfold chambers of rapamycin- and CsA-treated hamsters. Untreated animals served as controls. The angiogenic and inflammatory host tissue response to the mesh implants was then analyzed over a 14-day period by means of intravital fluorescence microscopy. Mesh incorporation was determined by histology and measurement of explantation strength. Rapamycin dose-dependently inhibited vascularization of implanted meshes, as indicated by a significantly reduced number of angiogenesis-positive regions of interest and microvessel density, when compared with CsA-treated hamsters and controls. In addition, the granulation tissue surrounding the meshes of rapamycin-treated animals exhibited only a low collagen content, resulting in an impaired mesh incorporation with a significantly reduced explantation strength. Leukocyte-endothelial cell interaction did not show marked differences between the observation groups. Thus, immunosuppressed patients should not be treated with rapamycin in case of incisional hernia repair in order to guarantee adequate mesh incorporation.