Abstract: Objective To explore the relationship among miR-144/451, reactive oxygen species(ROS)and AKT phosphorylation. Methods Cells from bone marrow(BM)and peripheral blood of wild-type mice(WT)and miR-144/451 knockout mice(miR-144/451^-/-, KO)were prepared. Flow cytometry was used to detect the level of ROS in erythroid cells, and Western blot was used to verify the protein level of phosphorylated AKT. Results Compared with that in WT mice, the level of ROS in erythroid cells in miR-144/451 KO mice significantly increased(P<0.05). The protein level of phosphorylated AKT increased significantly in nucleated erythroid cells from BM of miR-144/451 KO mice when compared to that in WT mice(P<0.05). Increased ROS level was the major cause of activation of AKT, while increased expression of 14-3-3ζ was the secondary cause of AKT phosphorylation. Conclusion The miR-144/451 suppresses AKT phosphorylation by reducing ROS level, and thus protects erythrocytes against oxidant stress.