The intestinal epithelial barrier is indispensable to our immune system. Defects in this barrier function have been observed in intestinal disorders such as inflammatory bowel diseases, food allergies, and celiac diseases. Therefore, the modulation of the barrier function is currently viewed as a potentially positive pharmacological outcome. This review describes a unique peptide, Asn-Pro-Trp- Asp-Gln (NPWDQ), which can finely adjust the intestinal barrier. It is obtained by the hydrolysis of casein, a major milk protein, and considerably inhibits the permeation of ovalbumin, one of the food allergens, in Caco-2, a human intestinal cell line. Using DNA microarray, we observed that NPWDQ only up-regulated expression of the occludin gene, whereas the levels of other genes, such as those of the claudin and zonula occludens families, remained unchanged. Increased protein expression of occludin was also observed. The fact that milk-derived peptide(s) can enhance intestinal barrier function gives a new significance to lactation because it plays an important role in promoting the maturation of the intestinal barrier. In this context, it is highly probable and worthy of considerable attention that various bioactive peptides with this type of activity are yet to be observed in the bovine and/or human casein sequence. Moreover, milkderived peptides could be considered as potential candidates for the prevention of certain intestinal disorders.