The use of synthetic mesh for ventral hernia repair is widely accepted, but mesh-induced inflammatory responses may lead to postoperative complications. Molecular mechanisms that direct the extent of the foreign body reaction to implanted materials are poorly understood. This study compares the influence of three macroporous meshes on the expression of genes critical for wound healing and extracellular matrix remodeling in a rat model. Full thickness abdominal wall defects were corrected with polypropylene, polyester, polytetrafluoroethylene (PTFE), or suture repair with no mesh. Explants were harvested 7 or 90 days after repair and were divided for histological, immunohistochemical, and mRNA analyses. Real-time quantitative polymerase chain reaction arrays were used to profile the expression of 84 genes involved in angiogenesis at the tissue-mesh interface. Evaluation of gene expression profiles and histologic specimens revealed that polypropylene and polyester induced a greater and more persistent inflammatory response than PTFE, which elicited a response most similar to that induced by suture repair. Mesh implantation induced the differential expression (>3-fold change and p < .01) of genes encoding inflammatory cytokines, growth factors, and extracellular matrix proteins relative to suture repair without mesh. Genes most markedly upregulated included the neutrophil chemoattractant CXCL2 and matrix metalloproteinases 3 and 9. Polyester induced the greatest number of differentially expressed genes relative to suture repair both at 7 and 90 days after implantation. Results from this study suggest that the particular type of mesh used in a hernia repair may affect the patient's wound healing response and clinical outcome.