Purpose: The manner in which surface roughness of implants affects bone-implant integration remains unknown. This study correlated morphologic profiles of bone-implant integration and extracellular matrix (ECM) gene expression in response to the placement of implants with different surface topographies. Materials and Methods: T-shaped hollow implants with turned and dual acid-etched (DE) surfaces were placed into rat femurs. A bone integration curve (BIC) was created from serial histomorphometric measurements within the implant chamber. The mRNA expression pattern of ECM genes in bone healing with or without implants was examined using reverse transcriptase-polymerase chain reaction. Results: At week 2, the BIC of the DE implant increased near the implant surface, whereas that of the turned implant decreased. The bone-to-implant contact rate of the DE implant was 6- and 2.5-fold higher than that of the tuned implant at weeks 2 and 4, respectively. A spatially standardized histomorphometry revealed that, at week 2, the DE implant had a greater bone volume than the turned implant in a zone near the implant, but not in zones distant from the implant surface. The DE implant evoked an accelerated mRNA expression for osteonectin and osteocalcin compared with the turned implant, along with an up-regulated expression for bone sialoprotein II, collagen III, and integrins in initial healing stages up to week 1. Discussion and Conclusion: The results indicate that different histologic bone integration profiles associated with increased surface roughness may be explained, in part, by the modulated expression of the selected ECM-related genes. The data provide evidence supporting the fact that gene regulation occurs at local levels of implant surfaces in vivo.