Animal guts are constantly exposed to various ingested microbes that trigger immune response. Prolonged infection causes gastrointestinal diseases in human. The Drosophila midgut has emerged as a useful model to study the homeostasis maintained by resident intestinal stem cells (ISCs) and their progeny, creating an active research field with prolific publications. In this study, we make a summing up of relevant researches of the mechanisms on the proliferation and differentiation of ISCs, meanwhile, we look far ahead into the prospect in this field, which make the theoretical base of the research for gut homeostasis in Drosophila.