Mesh implants as standard treatment for tissue defects can be adapted to patient's needs by specific bioactive coatings. The biophysical interaction with the surrounding tissue must be understood to describe the influence of coatings qualitatively and quantitatively. This study investigates the use of meshes to repair diaphragmatic defects. The physical stress in this tissue is high in comparison to other applications. Therefore, knowledge gained from this experimental model can be applied to other locations. Meshes were implanted on surgically created diaphragmatic defects in growing rabbits. A standardized load model was used to investigate 33 rabbits. The commercial products Ultrapro®, Surgisis®, and Proceed® were implanted. The adhesive properties of the meshes as well as the defect size were determined macroscopically at explantation after 4 months. Sections of the explanted meshes and diaphragms were examined histologically and immunohistochemically. The median defect size for all mesh groups decreased from the initial size of 10 mm down to 4.5 mm at explantation. No statistically significant differences were seen between the three mesh groups. Surgisis® was found to be completely disintegrated after 4 months. Ultrapro® and Proceed® showed no macroscopic differences compared to their original appearance. Both sealed the original diaphragmatic defect as tightly as at time of implantation. Histological and immunohistochemical analyses showed significant differences between the three mesh groups. Proceed® caused stronger inflammatory reaction in the surrounding tissue and inferior connective tissue formation. Regarding the composition of the newly generated tissue within the defect area, Ultrapro® and Surgisis® were found superior. This can sufficiently be explained by the different gradient of inflammatory reaction in the surrounding tissue. Because Surgisis® offers no sufficiently lasting support for the diaphragmatic defect, our future main focus for mesh modification is laid on Ultrapro®.