Blood–brain barrier (BBB) disruption is associated with tight junction protein degradation, basalmembrane disruption, and astrocyte damage. This study aims to investigate the role of matrix met-alloproteinase (MMP)-9 in BBB disruption during Angiostrongylus cantonensis infection. We used miceinfected with A. cantonensis, in which parasite-induced eosinophilia and inflammation might induceMMP-9 elevation. MMP-9 could cause claudin-5 degradation in endothelium tight junction, collagen typeIV degradation in basal membranes, and S100B degradation in astrocytes of wild-type mice. BBB perme-ability was significantly attenuated in MMP-9 knockout mice than in wild-type mice in angiostrongyliasismeningoencephalitis. Immune cell aggregates were also more attenuated in the brains of MMP-9 knock-out mice than in the brains of wild-type mice. Results suggest that MMP-9 activities are significant in BBBdisruption in angiostrongyliasis meningoencephalitis. This study improves understanding of molecularmechanisms that underlie brain invasion by A. cantonensis, which is a key step in the pathogenesis ofmeningoencephalitis, and can offer a new strategy to reduce mortality.