Background: To the Vypro II^® mesh, a large-pore-sized multifilamentous polypropylene mesh for hernia repair, supplementary polyglactin 910 multifilaments were added to improve intraoperative handling. As it has been suggested that polyglactin induces fibroplastic reactions and wound complications, this study was designed to evaluate the long-term tissue reaction to polyglactin in the Vypro II mesh. Materials and Methods: Two mesh materials, the Vypro II composite mesh (PP + PG) and the pure polypropylene variant (PP), were compared after inlay implantation in a standardized rodent animal model. After 14, 28, 42, 56, 84 and 112 days of implantation, histological analysis of the inflammatory response was performed: material absorption, inflammatory tissue reaction, fibrosis and granuloma formation were investigated. Results: Total absorption of polyglactin filaments of the Vypro II mesh occurred between 56 and 84 days of implantation. Both the inflammatory and the fibrotic reaction were initially increased in the PP + PG mesh group. These differences disappeared in the following implantation period. After 112 days, inflammation was even less pronounced in the PP + PG mesh group. Conclusion: The present data confirm a short-term polyglactin-induced increase in inflammation and fibrosis around implanted Vypro II meshes in rats. With regard to the long-term tissue response, even an anti-inflammatory property of polyglactin multifilaments in low-weight and large-pored polypropylene meshes cannot be ruled out.