**Abstract**

Fruit fly, *Drosophila melanogaster* is a most powerful animal model for exploring fundamental biological processes and modeling molecular and cellular aspects of human diseases. It provides the flexibility and tool box with which scientists can experimentally manipulate and study behavior as well as gene expression in specific, defined population of cells in their normal tissue contexts. The utility and increasing value of a sophisticated genetic system of flies, the tool box available for studying physiological function, functional imaging, neural circuitry from gut to brain, taste receptors expression and controlling gene expression by determining the specific cells in the intestine, makes fly gut the most useful tissue for studying the regulation of feeding behavior under changing internal state. To understand the intestine and its connectivity with the brain, *Drosophila* has proved an ideal model organism for studying gut brain axis aspects of human metabolic diseases. Various markers and fly lines are available to characterize the expression of transgenes in the intestine. The newly generated genetic tools aim to streamline the design of experiments to target specific cells in intestine for genetic manipulations based on their type and location within physiologically specialized intestinal regions. This chapter will be useful for understanding post-ingestive sensing system that mediate food preferences and to investigate fundamental biological processes and model human diseases at the level of single cells in the fly gut. Furthermore, the utility of adult fly gut can be extended to the study of dietary and environmental factors relevant to health and disease by screening for cells and micro circuits stimulated by internal state or the consumption of various nutrients.

**Keywords:** gut brain axis, *Drosophila*, taste receptors, enterocytes, enteroendocrine cells
