Immune responses are regulated by gut environmental factors, including diet and microbiota. Here, we show our recent findings of the emerging roles of w3 and w6 essential fatty acid metabolites in the regulation of immunity, allergy and inflammation, and their involvement with intestinal microbes. We found that dietary linseed oil which is high in w3 a-linolenic acid ameliorated allergic and inflammatory symptoms through conversion to potent anti-allergic and anti-inflammatory lipid metabolites, including 17,18-epoxyeicosatetraenoic acid and 12-hydroxyeicosapentaenoic acid. Further, we recently found that 10-oxo-cis-12-cis-15-octadecadienoic acid (aKetoA) was produced by intestinal microbes, and acted as a novel postbiotic derived from a-linolenic acid for the control of contact hypersensitivity and diabetic adipose tissue inflammation. We also found that w6 fatty acid metabolism is a key factor for the establishment of oral vaccine through mediating innate immune signal from intestinal microbes. These results indicate that the metabolism of essential fatty acid plays crucial roles in the regulation of immunity, allergy and inflammatory diseases.