Acute inflammation is essential for initiating and coordinating the body’s response to injuries and infections. However, in acute inflammatory diseases, inflammation is not resolved but propagates further, which can ultimately lead to tissue damage such as in sepsis, acute respiratory distress syndrome and deep vein thrombosis. Currently, clinical protocols are limited to systemic steroidal treatments, fluids and antibiotics that focus on eradicating inflammation rather than modulating it. Strategies based on stem cell therapeutics and selective blocking of inflammatory molecules, despite showing great promise, still lack the scalability and specificity required to treat acute inflammation. By contrast, polymeric particle systems benefit from uniform manufacturing at large scales while preserving biocompatibility and versatility, thus providing an ideal platform for immune modulation. Here, we outline design aspects of polymeric particles including material, size, shape, deformability and surface modifications, providing a strategy for optimizing the targeting of acute inflammation.