摘要： Oxidative stress and apoptosis in retinal pigment epithelium cells are involved in the pathogenesis of diabetic retinopathy (DR). Forkhead box class O 6 (FOXO6) is a member of the FOXO family that can regulate diabetes‐induced oxidative stress. However, the role of FOXO6 in DR has not been clarified. The aim of the present study was to investigate the effects of FOXO6 on high glucose (HG)‐induced oxidative stress and apoptosis in ARPE‐19 cells. The results showed that FOXO6 was overexpressed in clinical vitreous samples from DR patients and in HG‐induced ARPE‐19 cells. Knockdown of FOXO6 by small interfeing RNA targeting FOXO6 (si‐FOXO6) mitigated the HG‐induced the production of reactive oxygen species and malondialdehyde, as well as the inhibition of superoxide dismutase activity. Knockdown of FOXO6 reduced the rate of cell apoptosis in HG‐induced ARPE‐19 cells. The increase in bax expression and decrease in bcl‐2 expression caused by HG stimulation were reversed by si‐FOXO6 transfection. Furthermore, knockdown of FOXO6 enhanced the activation of Akt/Nrf2 pathway in HG‐stimulated ARPE‐19 cells. Taken together, suppression of FOXO6 protects ARPE‐19 cells from HG‐induced oxidative stress and apoptosis, which is in part mediated by the activation of Akt/Nrf2 pathway.