Neutrophils are usually the first innate cell to arrive in high numbers at foci of cell damage or infection, but other myeloid lineage cells, in particular, inflammatory monocytes are also recruited in high numbers that accumulate over several days. Importantly, although these monocytes effectively kill pathogens, clear cell debris and remodel damaged tissue, large numbers of their precursors, released from the bone marrow in response to signals from the inflammatory focus, may cause significant damage to nearby healthy tissue. This increases tissue scarring and reduces function and/or may be lethal in the short or long term. Using a variety of murine models of macrophage-mediated disease, including fatal infectious diseases, such as flaviviral encephalitis or severe malaria, autoimmune diseases like experimental autoimmune encephalomyelitis (EAE), non-infectious diseases such as myocardial infarction and kidney transplantation, where ischaemia-reperfusion injury are prominent, as well as inflammatory bowel disease, we have shown that reducing inflammatory monocyte recruitment to the inflammatory site reduces tissue destruction and clinical disease signs, improves healing and increases survival. Intravenously infused, negatively-charged, immune-modifying microparticles (IMP) are recognized by scavenger receptors on inflammatory monocytes and phagocytosed, clearing IMP from the blood. IMP-containing monocytes display phosphatidylserine and thus become sequestered by the spleen, reducing the numbers that migrate to the inflamed site. This reduces adventitious tissue damage, enables healing and improves survival without interfering with adaptive immunity. This approach has enabled us to better understand the kinetics of normal tissue damage and regeneration, but also holds significant promise in a variety of macrophage-mediated diseases and our efforts are currently aimed at translating this into the clinical setting.