Bioactive coating on bone and dental implants is widely used to increase their integration with the host tissue, with millions of implantations performed globally each year. Numerous coating strategies focus on creating a cell-adhesive surface by employing bone matrix components, but insufficient integration and its associated complications remain a substantial clinical challenge. Designing an implant coating to more comprehensively promote healing while appropriately modulating host immune response is still an unfulfilled promise. This study reports the development of a polysaccharide coating that can improve osseointegration by targeting and regulating inflammatory activity at the implant surface. Zymosan-a fungal component-is screened and covalently grafted onto titanium (Ti) substrates. The zymosan coating specifically stimulates macrophages through toll-like receptors into a proregenerative phenotype, which produces abundant osteogenic/angiogenic cytokines to enhance osteogenic activities locally. Further assessment in a rat femur condyle defect indicates that zymosan coated at a medium dose (0.1 mu g mm(-2)) remarkably increases the integration of Ti column with bone tissue, causing no abnormality to the host. This is the first demonstration that modulating inflammation with an immunoactive coating material can promote bone-implant integration, which may inspire new strategies for the design of bone and dental implants.