Objective To study the protective effects and mechanism of Schisandrin B（SchB）in the oxidative injury of human retinal pigment epithelial cells（ARPE-19）induced by H,2,O,2,.Methods ARPE-19 cells model with oxidative injury were induced by H,2,O,2,.Cell viability, apoptosis, ROS generation and miR-374 a level were measured by CCK-8 assay, flow cytometry assay, DCFH-DA staining and RT-qPCR, respectively.Expressions of proteins associated with viability, apoptosis and oxidative stress, as well as PI3 K/AKT and MEK/ERK pathways was measured by western blotting.Results H,2,O,2, reduced the cell viability obviously while it promoted apoptosis and oxidative stress in ARPE-19 cells.SchB ameliorated H,2,O,2,-induced cell injury.The expression of miR-374 a was up-regulated by SchB in H,2,O,2,-treated cells, and miR-374 a inhibition obviously reversed the effects of SchB in H,2,O,2,-treated cells.Finally, the PI3 K/AKT and MEK/ERK pathways were inhibited by SchB through up-regulation of miR-374 a.Conclusion SchB can protect ARPE-19 cells against H,2,O,2,-induced injury through up-regulation of miR-374 a and inhibition of PI3 K/AKT and MEK/ERK pathways.SchB might become a potential therapeutic drug for retinopathy.