The implantation of a non-absorbable polypropylene mesh during hernia repair causes chronic foreign body reaction involving the surrounding tissue. In case of inguinal hernia repair using mesh techniques, the spermatic cord is potentially affected by this chronic inflammatory tissue remodeling. This effect has been investigated using standardized animal models (pig and rabbit). Fifteen adult male pigs underwent transinguinal preperitoneal implantation of a polypropylene mesh. The contralateral side with a Shouldice repair served as control. After 7, 14, 21, 28, and 35 days, three animals were sacrificed. The spermatic cords were resected and analyzed histologically. In a second experiment Lichtenstein repair using the same polypropylene mesh and Shouldice repair on the contralateral side was done in eight chinchilla rabbits. Three animals served as controls. Three months after operation, the analysis included testicular size, testicular temperature, and testicular and spermatic cord perfusion. We added histological evaluation of the foreign body reaction and the spermatogenesis using the Johnsen score. In the pig, we observed a certain foreign body reaction with diffuse infiltrating inflammatory cells after mesh implantation. Venous thrombosis of the spermatic veins occurred in five of 15 cases. One animal presented focal fibrinoid necrosis of the deferent duct wall. The side of Shouldice repair showed only minor postoperative changes. In the rabbit, we also observed a typical foreign body reaction at the interface between mesh and surrounding tissue, which was not detectable after Shouldice repair. The mesh repair led to a decrease of arterial perfusion, testicular temperature, and the rate of seminiferus tubules with regular spermatogenesis classified as Johnsen 10 (Lichtenstein: 48.1%, Shouldice: 63.8%, controls: 65.8%). Testicular volume increased about 10% after each operation. The implantation of a polypropylene mesh in the inguinal region induces major response of the structures of the spermatic cord. This may have an influence also on spermatogenesis. Due to this a strict indication for implantation of a prosthetic mesh during inguinal hernia repair is recommended.