Abstract The implantation of medical devices often triggers several immune responses, one kind of which is categorized as foreign body reactions. It is well established that macrophages and many other cells participate in the complex processes of foreign body reactions, and cause severe inflammations and fibrotic capsule formation in surrounding tissues. However, the detailed mechanisms of macrophage responses, recruitment and activation, in foreign body reactions are not totally understood. In the meantime, mathematical models have been proposed to systematically decipher the behavior of this complex system of multiple cells, proteins and biochemical processes in wound healing responses. Based on these early works, this study introduces a mathematical model in two spatial dimensions to investigate the transient behavior of macrophages, fibroblasts and their interactions during the formation of fibrotic tissue. We find that the simulation results are consistent with the experimental observations. These findings support that the model can reveal quantitative insights for studying foreign body reaction processes.