Granzyme A (GrA) is a serine protease produced in cytotoxic lymphocytes, lung epithelial cells (alveolar type-II cells), and alveolar macrophages. In the present study, recombinant rat GrA (rGrA) was found to cause rounding and detachment of an alveolar type-II epithelial cell line, A549. Also, rGrA stimulated release of a neutrophil chemoattractant, interleukin-8, from the cells, via a mechanism involving microtubule disruption, probably resulting from reduction of cell adhesion to culture dishes. These findings suggest that GrA might be involved in the pathogenesis of certain lung diseases characterized by loss of alveolar wall structures, neutrophil accumulation, and chronic inflammation.