Abstract: The intensification of aquaculture and climate change have amplified hypoxic stress in aquatic environments, while arachidonic acid (AA) may have the potential to alleviate hypoxic stress. This study investigated the role of AA metabolism in hypoxia adaptation, focusing on hepatic angiogenesis and antioxidant responses in largemouth bass (Micropterus salmoides). Hypoxic stress significantly impaired hepatic antioxidant capacity, evidenced by reduced total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and catalase (CAT) activities, alongside elevated malondialdehyde (MDA) levels (P<0.05). Hypoxic stress significantly increased whole-blood hemoglobin and methemoglobin levels (P<0.05), induced structural changes in gill tissues such as reduced interlamellar cell masses and elongated lamellae. Concurrently, hypoxia activated hepatic angiogenesis, upregulating vegfa, mmp2, jagged, and notch1 expression (P<0.05), and induced hepatic lipid metabolic reprogramming, characterized by increased saturated fatty acid (SFA) and decreased polyunsaturated fatty acid (PUFA) levels (P<0.05). However, AA exhibited a unique accumulation pattern, suggesting its potential involvement in hypoxia adaptation regulation. Exogenous AA supplementation reduced the asphyxiation point from 1.08 to 0.5 mg/L, prolonged hypoxia survival time, and enhanced hepatic T-AOC, SOD, and CAT activities (P<0.05). While gill structural changes under hypoxia remained unaffected, hepatic angiogenesis was markedly potentiated, as demonstrated by intensified vascular networks and robust upregulation of vegfa, vegfr2, mmp2, jagged, and notch1 (P<0.05). Mechanistically, AA metabolism generated pro-angiogenic mediators, including prostaglandin E₂ (PGE₂) and epoxyeicosatrienoic acids (EETs), which synergistically activated angiogenic pathways (P<0.05). This study demonstrates that largemouth bass employs hypoxia-induced lipid metabolic remodeling to promote hepatic AA accumulation, which is subsequently metabolized into PGE₂ and EETs to activate angiogenesis pathways, forming a unique adaptive strategy against hypoxic stress. These findings establish a novel link between AA metabolism and angiogenesis in fish hypoxia adaptation, providing a scientific foundation for dietary interventions to mitigate hypoxic challenges in aquaculture.