Magnesium alloys have been used to manufacture biodegradable implants, bone graft substitutes, and cardiovascular stents. WE43 was the most widely used magnesium alloy. The degradation process begins when the magnesium alloy stent is implanted in the body and comes into contact with body fluid. The degradation products include hydrogen, Mg2+, local alkaline environment, and unsoluble products. A large number of studies focused on Mg2+ and pH in vitro, and in vivo of magnesium alloys, but few studies on unsoluble corrosion products (UCPs). In this study, UCPs of WE43 alloy were prepared by immersion in vitro, and their effects on macrophages were investigated. The results showed that the unsoluble corrosion products were Mg24Y5, Mg12YNd, and MgCO3·3H2O, which were dose‐dependent on the apoptosis and necrosis of macrophages. After phagocytosis of UCPs, macrophages mainly metabolize in lysosome, and autophagy also participates in the metabolism of UCPs. It also decreases mitochondrial membrane potential and increases lysosomes, endoplasmic reticulum stress, and P2X7 receptor activation. These will increase reactive oxygen species (ROS) in cells, activating NLRP3 inflammatory corpuscles, activating the downstream pro‐IL18 and pro‐IL1β, and converting it to IL‐18, and IL‐1β. However, its pro‐inflammatory effect is far lower than that of the classical Lipopolysaccharide (LPS) pro‐inflammatory pathway. This work has increased our understanding of magnesium alloy metabolism and provides new ideas for the clinical application of magnesium alloys.