Innate immunity is a universal prophylactic system which all multi-cellular animals possess. Macrophages are the cells that play the central role in the innate immune system. In 1991, we discovered a substance in a water extract of wheat flour that activated macrophages after oral or intradermal administration. The active substance was lipopolysaccharide (LPS), which is derived from the cell walls of Pantoea agglomerans, gram-negative bacteria that grows symbiotically with wheat. We named the substance IP-PA1 (immuno potentiator from P. agglomerans, former name: LPSp). The IP-PA1 is considered to be useful in various fields such as health food (to prevent and improve metabolic syndromes), skincare products (to maintain healthy skin, to improve atopic dermatitis, and to resist aging), and as active ingredients in feeds for stockbreeding and aquaculture (to act as a defense against infection). In this manuscript, we discuss the significance of activation of macrophages through oral or intradermal administration, the discovery of IP-PA1 as a macrophage-activating substance, the chemical structure of IP-PA1, the use of IP-PA1 to improve various disorders, the mechanism of action, and the possibility of application of IP-PA1 to various fields.