ABSTRACT: To study Megalobrama amblycephala adaption to water hypoxia, the changes in physiological levels, innate immune responses, redox balance of M.amblycephala during hypoxia were investigated in the present study. When M. amblycephala were exposed to different dissolved oxygen (DO) including control (DO: 5.5 mg/L) and acute hypoxia (DO: 3.5 and 1.0 mg/L, respectively), hemoglobin (Hb), methemoglobin (MetHb), glucose, Na+, succinatedehydrogenase (SDH), lactate, interferon alpha (IFN?), and lysozyme (LYZ), except hepatic glycogen and albumin gradually increased with the decrease of DO level. When M. amblycephala were exposed to different hypoxia time including 0.5 and 6 h (DO: 3.5 mg/L), and then reoxygenation for 24 h after 6 h hypoxia, Hb, MetHb, glucose, lactate, and IFN?, except Na+, SDH, hepatic glycogen, albumin, and LYZ increased with the extension of hypoxia time, while the above investigated indexes (except albumin, IFN?, and LYZ) decreased after reoxygenation. On the other hand, the liver SOD, CAT, hydrogen peroxide (H2O2), and total ROS were all remained at lower levels under hypoxia stress. Finally, Hif-1? protein in the liver, spleen, and gill were increased with the decrease of oxygen concentration and prolongation of hypoxia time. Interestingly, one Hsp70 isoforms mediated by internal ribozyme entry site (IRES) named junior Hsp70 was only detected in liver, spleen and gill. Taken together, these results suggest that hypoxia affects M. amblycephala physiology and reduces liver oxidative stress. Hypoxia-reoxygenation stimulates M. amblycephala immune parameter expressions, while Hsp70 response to hypoxia is tissue-specific.