Background: Macrophages robustly secrete MMP-9 upon activation, and mechanisms for active delivery of MMP-9 vesicles to the cell surface have not been described. Results: MMP-9 is packaged into unique ER protein-containing vesicles that associate with microtubule motors in activated macrophages. Conclusion: Macrophage activation requires enhanced microtubule stabilization for rapid secretion of up-regulated MMP-9. Significance: Understanding the nature and mechanisms of intracellular trafficking of MMP-9 is relevant to both immunology and cancer biology fields.