The study identifies a novel pathway involving the biosynthesis of potent anti-inflammatory and pro-resolving mediators from docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulate 17-hydroxydocosahexaenoic acid (17-HDHA) and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S-HDHA), which are converted by MΦs into novel dihydroxy-containing products with potent anti-inflammatory and pro-resolving activities. These products, named maresins, enhance resolution by reducing neutrophil infiltration and stimulating MΦ phagocytosis. The findings suggest that maresins and the new metabolome may play a role in tissue homeostasis, inflammation resolution, wound healing, and host defense. The study also highlights the importance of omega-3 fatty acids and their role in various biological processes, providing potential therapeutic targets for inflammatory and related diseases.The study identifies a novel pathway involving the biosynthesis of potent anti-inflammatory and pro-resolving mediators from docosahexaenoic acid (DHA) by macrophages (MΦs). During the resolution of mouse peritonitis, exudates accumulate 17-hydroxydocosahexaenoic acid (17-HDHA) and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S-HDHA), which are converted by MΦs into novel dihydroxy-containing products with potent anti-inflammatory and pro-resolving activities. These products, named maresins, enhance resolution by reducing neutrophil infiltration and stimulating MΦ phagocytosis. The findings suggest that maresins and the new metabolome may play a role in tissue homeostasis, inflammation resolution, wound healing, and host defense. The study also highlights the importance of omega-3 fatty acids and their role in various biological processes, providing potential therapeutic targets for inflammatory and related diseases.