α-Linolenic acid (ALA) and its non-enzymatic oxidized products, namely, phytoprostanes and phytofurans, are found in some nuts. The uptake and deposition of these compounds are not well-defined. Walnut has high ALA and a considerable amount of phytoprostanes and phytofurans compared to other common nuts. When fed to rodents, ALA and eicosapentaenoic acid levels increased in the liver and heart tissues compared to the control diet. Furthermore, phytoprostanes and phytofurans were elevated 3fold in both tissues after a walnut diet, indicating that they are not only contributed from the diet but also generated through in vivo autoxidation of ALA found in the walnuts. It was further noted that a walnut diet reduced 5-F 2t-isoprostanes and 12hydroxyeicosatetraenoic acid and induced 4-F 4t-neuroprostane and significant amounts of anti-inflammatory hydroxydocosahexaenoic acid in the liver only. Altogether, high ALA in a walnut diet elevated phytoprostanes and phytofurans in the liver and heart tissues and showed the regulation of anti-inflammatory lipid mediators in the liver only.