In this study, we found that during bacterial infection, ZnONPs enhance the antibacterial property of PMNs, alleviate subcutaneous immune cell infiltration in vivo, enhance PMNs migration, improve bacterial phagocytosis efficiency of PMNs, promote PMNs to express the proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and facilitate reactive oxygen species (ROS) production of PMNs. Here, TNF is linked to bacterial infectious disease.