Introduction: When a suture is placed in a patient the foreign body reaction (FBR) is initiated. The tissue response to a foreign body following implantation of a biomaterial leads to matrix deposition and fibrous encapsulation. This process is overlaid by the same inflammatory response triggered by any acute wound and if the foreign body is left in situ develops into a “chronic wound”. This pathway is of obvious interest to the surgeon (and patient) in terms of pathological process that may result in fibrosis, adhesions, contractures, excessive scarring and even failure of implanted devices. So far the study of complex interactions between cells and molecules during FBR has been limited due to the lack of live in vivo imaging opportunities. The genetic tractability of the zebrafish combined with its translucency and amenability for imaging make it an excellent candidate model organism for studying the mechanisms underlying FBR. Methods: An 8-0 nylon or vicryl suture was placed anterior to the tail fin of a wild type or transgenic adult zebrafish expressing various fluorescent reporter genes. A small “pull through” wound simulated the acute condition as a control. Macrophage, neutrophil, blood vessel and inflammatory cytokine response to the site was visualised upto 28days. The colony stimulating factor 1 receptor (csf1ra) mutant zebrafish was used, which has a limited immune response. Confocal and multiphoton microscopy was used to capture images. Results: Real time in vivo imaging analysis showed a prolonged and exaggerated inflammatory response to a suture compared to an acute wound. The inflammatory response is exaggerated and extended with increased numbers of macrophages, many of which have assumed a foreign body giant cell-like phenotype near the suture. We also observe a higher number, and increased activity, of neutrophils around the suture compared to an acute wound- this is maintained for the full 28days of our study. The observed inflammatory response to the more bio-reactive vicryl suture was exacerbated in comparison to the less immune-stimulating nylon suture. We also observe an avascular region adjacent to the foreign body, not maintained in acutely wounded fish. The avascular zone correlates with a fibrous encapsulated region surrounding the suture. In immune deficient fish we see a more limited FBR and thus smaller avascular zone. Implications: This excessive inflammatory response may be contributing towards adverse outcomes associated with FBR such as fibrosis and scarring. We can gain mechanistic insight into inflammation, the FBR avascular zone and excessive matrix deposition around a foreign body in real time using the zebrafish model. We have shown that the bio-reactivity of a material dictates the scale of FBR and that the host response also modifies this. This has implications for the use and design of surgically implantable devices.