Maresins are novel macrophage-derived mediators with potent anti-inflammatory and pro-resolving properties. The study identifies a new pathway for the biosynthesis of these mediators from docosahexaenoic acid (DHA) by macrophages (MΦs) during the resolution of inflammation. Using lipidomics and proteomics, researchers found that during mouse peritonitis, exudates contained 17-hydroxydocosahexaenoic acid (17-HDHA) and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S-HDHA), which are markers of resolvin (Rv) and protectin biosynthesis. When added to activated MΦs, these substrates were converted into novel dihydroxy-containing products with anti-inflammatory and pro-resolving activity similar to RvE1, protectin D1, and other known mediators. The study identified a novel 14-lipoxygenase pathway that generates bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, termed maresin, which enhances inflammation resolution. These findings suggest that maresins and their associated metabolome may play a role in the beneficial effects of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense. The study also highlights the importance of DHA in the biosynthesis of these mediators and the potential therapeutic applications of maresins in inflammatory diseases. The research provides insights into the mechanisms of inflammation resolution and the role of macrophages in this process.Maresins are novel macrophage-derived mediators with potent anti-inflammatory and pro-resolving properties. The study identifies a new pathway for the biosynthesis of these mediators from docosahexaenoic acid (DHA) by macrophages (MΦs) during the resolution of inflammation. Using lipidomics and proteomics, researchers found that during mouse peritonitis, exudates contained 17-hydroxydocosahexaenoic acid (17-HDHA) and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S-HDHA), which are markers of resolvin (Rv) and protectin biosynthesis. When added to activated MΦs, these substrates were converted into novel dihydroxy-containing products with anti-inflammatory and pro-resolving activity similar to RvE1, protectin D1, and other known mediators. The study identified a novel 14-lipoxygenase pathway that generates bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, termed maresin, which enhances inflammation resolution. These findings suggest that maresins and their associated metabolome may play a role in the beneficial effects of DHA and MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense. The study also highlights the importance of DHA in the biosynthesis of these mediators and the potential therapeutic applications of maresins in inflammatory diseases. The research provides insights into the mechanisms of inflammation resolution and the role of macrophages in this process.