The small intestine plays a crucial role in digestion and nutrient absorption; but in constant competition with a plethora of microbes and their toxins which are part of the normal intestinal flora. As the physical boundary between the outside and inside environments, the intestinal epithelium came from stem cells; and then migrate toward the apex of the villus from where they slough off. The epithelium of the adult mammalian intestine is in constant dynamic interaction with its underlying mesenchyme controlling direct progenitor proliferation, lineage commitment, terminal differentiation, and ultimately cell death. Human Small intestine epithelial cells are potentially a suitable model for stablishing disease models; such as inflammatory bowel disease, colitis, intestinal cancer, intestinal infections. They are important tools also and more importantly in toxicity and drug discovery.