Stem cell-mediated tissue repair is a promising approach for many diseases. Mammalian intestine is an actively regenerating tissue such that epithelial cells are constantly shedding and underlying precursor cells are constantly replenishing the loss of cells. An imbalance of these processes will lead to intestinal diseases including inflammation and cancer. Mammalian intestinal stem cells (ISCs) are located in bases of crypts but at least two groups of cells have been cited as stem cells. Moreover, precursor cells in the transit amplifying zone can also proliferate. The involvement of multiple cell types makes it more difficult to examine tissue damage response in mammalian intestine. In adult Drosophila midgut, the ISCs are the only cells that can go through mitosis. By feeding pathogenic bacteria and stress inducing chemicals to adult flies, we demonstrate that Drosophila ISCs in the midgut can respond by increasing their division. The resulting enteroblasts, precursor cells for enterocytes and enteroendocrine cells, also differentiate faster to become cells resembling enterocyte lineage. These results are consistent with the idea that Drosophila midgut stem cells can respond to tissue damage induced by pathogens and initiate tissue repair. This system should allow molecular and genetic analyses of stem cell-mediated tissue repair. J. Cell. Physiol. 220: 664–671, 2009. © 2009 Wiley-Liss, Inc.