Interleukin-1 Receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory cytokine that inhibits IL-1 activity. Daily subcutaneous injection is currently approved by the Food and Drug Administration (FDA) to treat rheumatoid arthritis and neonatal-onset multisystem inflammatory disease. However, the short half-life and high concentration required to inhibit IL1 activity may limit its use in clinic to treat other IL-1 mediated pathologies. Many strategies have been developed to improve the efficacy of IL-1Ra, but none have been granted FDA approval. In this thesis, we examine the use of microparticles (MPs) to deliver IL-1Ra to inhibit IL-1 activity. We found MPs efficiently bind and release IL-1Ra. In vitro assays and in vivo studies show that IL-1Ra released from MPs is biologically active and can inhibit IL-1 activity. When IL-1Ra MPs were injected subcutaneously into a murine model, serum IL-1Ra was elevated and IL-1 activity was inhibited for an extended time when compared to a bolus injection of soluble IL-1Ra. A novel MP formulation was created which layered IL-1Ra throughout the coating, resulting in higher loading capacity, limited burst release, and longer IL-1 inhibition in vivo. When locally applied after rat medial collateral ligament (MCL) injury, IL-1Ra loaded MPs significantly increased the local concentration of IL-1Ra while having little impact on the systemic concentration. IL-1Ra loading onto microparticles significantly reduced inflammation caused by the microparticles themselves, indicating the IL-1Ra was active. Further, microparticles did not induce a foreign body response and decreased the immunogenicity of human IL-1Ra in a healing rat MCL. A novel microparticle which incorporates superparamagnetic iron oxide (SPIO) was found to be trifunctional:​ it can deliver protein, be tracked using magnetic resonance imaging, and can be manipulated with a magnetic field. Overall, this thesis demonstrates microparticles can systemically or locally deliver an active therapeutic protein for an extended time.