Accumulation of pathological tau protein is a hallmark of Alzheimer's disease, spreading from the entorhinal cortex to the hippocampal region. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology but their role in tau propagation is unclear. This study developed an adeno-associated virus-based model showing rapid tau propagation from the entorhinal cortex to the dentate gyrus within 4 weeks. Depleting microglia significantly suppressed tau propagation and reduced excitability in the dentate gyrus. Microglia spread tau via exosome secretion, and inhibiting exosome synthesis reduced tau propagation in vitro and in vivo. These findings suggest that microglia and exosomes contribute to tauopathy progression, with the exosome secretion pathway potentially being a therapeutic target.Accumulation of pathological tau protein is a hallmark of Alzheimer's disease, spreading from the entorhinal cortex to the hippocampal region. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology but their role in tau propagation is unclear. This study developed an adeno-associated virus-based model showing rapid tau propagation from the entorhinal cortex to the dentate gyrus within 4 weeks. Depleting microglia significantly suppressed tau propagation and reduced excitability in the dentate gyrus. Microglia spread tau via exosome secretion, and inhibiting exosome synthesis reduced tau propagation in vitro and in vivo. These findings suggest that microglia and exosomes contribute to tauopathy progression, with the exosome secretion pathway potentially being a therapeutic target.