Macrophages are immune sentinels that constantly survey tissue environments to detect and destroy foreign pathogens. The cell surface of macrophages is replete with dynamic endocytosis and trafficking events, which aid pathogen detection and immune responses. Macropinosomes are responsible for sampling the environment and pathogen uptake and we have shown that they are also key sites for pathogen detection and signalling by Toll-like receptors (TLRs). We have further characterised endocytic cargo and molecular machinery associated with these compartments. The common endocytic receptor, low density lipoprotein-like receptor 1(LRP1), has previously been implicated in inflammation. We show that LRP-1 is phosphorylated in LPS-activated cells and imaging shows that it traffics through macropinosomes and other endosomes in LPS-induced recycling trajectories. The sorting and routing of LRP-1 is controlled in part by its binding to different sorting nexin (SNX) proteins and biochemical and imaging approaches reveal divergent trajectories for SNX-LRP-1 complexes in activated macrophages. LRP-1 has key roles in neuro-inflammation and our studies extend to comparing results in mouse macrophages and microglial cells. To better manage inflammation in disease it is important that we further investigate LRP1 and define its role in signalling and trafficking downstream of TLRs.