The complete stereochemistry of MaR1 has been established, and MaR1 also displays potent tissue regenerative as well as anti-nociceptive actions. In the Mazindol present manuscript, we identified and cloned the human macrophage 12-LOX involved in the biosynthesis and bioactive maresin L-655,708 metabolome, and found a new member of the maresin family produced from DHA. The human macrophage 12-LOX converted both AA and DHA with essentially equivalent efficiency to produce the hydroperoxy products, respectively, that were predominantly in the carbon 14 with S configuration. A new 13R,14S-diHDHA was identified from human macrophages that displayed potent anti-inflammatory and pro-resolving actions. Production of 13R,14S-diHDHA involved the initial oxygenation at C-14 followed by 12-LOX-catalyzed epoxidation and subsequent hydrolysis via sEH. The proposed biosynthetic schemes of MaR1 and 13R,14S-diHDHA are summarized in Fig. 7. Given the potent anti-inflammatory and pro-resolving actions of the new 13R,14S-diHDHA diol and its biosynthesis from the 13S,14Sepoxy- maresin, we coined this product as MaR2. Maresins are biosynthesized by human macrophages 12-LOX from DHA. MaR1 is the first member of this family to be identified. In addition to its anti-inflammatory, pro-resolving, tissue regenerative and anti-nociceptive actions, MaR1 was recently found to dampen the pro-inflammatory response to organic dust in bronchial epithelial cells, and attenuates mouse colitis. MaR1 was also identified in human synovial fluid from rheumatoid arthritis patients. Another related 12- LOX-derived product, 14S,21R-diHDHA, was shown to enhance wound healing and rescues mesenchymal stem cell function in diabetes and renal ischemia/reperfusion injury. In the present manuscript, we identified a novel member of the maresin family, namely 13R,14S-diHDHA, coined MaR2, that is produced by the human 12-LOX and sEH in human macrophages. MaR2 exhibited similar potency to MaR1 in limiting PMN infiltration, but had an apparent optimal concentration 2�C3 log orders lower than MaR1 in enhancing human macrophage phagocytosis of zymosan. MaR2 also enhanced human macrophage uptake of apoptotic PMN, but was less potent than MaR1.