The intestinal epithelial cells are replaced in every three to four days. This system is maintained by self-reproduction, differentiation of the intestinal stem cells. The continuous monolayer of intestinal epithelial cells functions in innate immunity as the primary barrier against microbial colonization. Paneth cells secrete α-defensins, and they are actively involved in the innate immunity and maintain the intestinal homeostasis by controlling intestinal microbiota. In addition, recent analyses of epithelial renewal in the intestine illustrate that Paneth cells provide survival signals to crypt intestinal stem cells. Two types of intestinal stem cells, crypt base columnar (CBC) stem cell and +4 stem cell, have been identified. Lgr5 positive CBC stem cells, Bmi1 positive +4 stem cells and Paneth cells create the stem cell niche in the small intestine. In this review, recent advances in understanding the roles of Paneth cells and stem cells which involve stem cell niche, and their association of inflammatory bowel disease were discussed and summarized.