Host-biomaterial interactions are critical determinants of the success or failure of an implant. However, detailed understanding of this process is limited due to a lack of dynamic tools for in vivo analyses. Here we characterize host-biomaterial interactions in zebrafish (Danio rerio), which are optically translucent and genetically tractable. Histological and immunohistochemical analyses following polypropylene suture implantation into adult zebrafish showed prolonged elevation of immune cell recruitment and collagen deposition, resembling a foreign body response. Live in vivo analysis showed that adsorption of the immunomodulatory cytokine interleukin-10 to a polystyrene microparticle, microinjected into transgenic larval zebrafish, inhibited neutrophil recruitment after 24 h compared to control microparticles, with no change in macrophage recruitment. This study illustrates that zebrafish are useful to investigate host-biomaterial interactions and have potential for high-throughput analysis of novel immunomodulatory biomaterials.