Objective To observe and preliminarily explore the effect of mogroside on oxidative stress of retinal pigment epitheliaum (RPE) cells induced by hydrogen peroxide (H2O2) and its possible mechanism. MethodsA experimental study. The RPE cells were divided into control group, H2O2 group, silent information regulator of transcription 1 (SIRT1) inhibitor EX527 group (EX527 group), mogroside group, mogroside+EX527 group. Methyl thiazolete trazolium method was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis rate. 2',7'-dichlorodihydrofluorescein diacetate fluorescent probe method, xanthine method and enzyme-linked immunosorbent assay method were used to detect the level of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cells respectively. Real-time quantitative polymerase chain reaction and Western blot were used to detect relative expressions of SIRT1, nuclear factor erythroid-2-related actor 2 (Nrf2), heme oxygenase-1 (HO-1) mRNA and protein in cells. One-way ANOVA was used for comparison among groups. The pairwise comparison between groups was tested by the least significant difference t test. Results Compared with the control group, the H2O2 group cell survival rate decreased, the apoptosis rate increased, the ROS level in the cells increased, the SOD activity decreased, the MDA content increased, and the relative expression of SIRT1, Nrf2, HO-1 mRNA and protein decreased (P＜0.05). Compared with H2O2 group, the cell survival rate decreased, apoptosis rate increased, the cell ROS level increased, SOD activity decreased, MDA content increased, SIRT1, Nrf2, HO-1 mRNA and protein expression decreased in EX527 group (P＜0.05); the cell survival rate increased, apoptosis rate decreased, ROS level decreased, SOD activity increased, MDA content decreased, and the relative expression of SIRT1, Nrf2, HO-1 mRNA and protein increased in mogroside group (P＜0.05). Compared with the mogrosides group, the cell survival rate decreased, the apoptosis rate increased, the level of ROS increased, SOD activity decreased, MDA content increased, SIRT1, Nrf2, HO-1 mRNA and protein decreased in mogrosides+EX527 group (P＜0.05). ConclusionsMogrosides can alleviate the oxidative stress response of visual RPE cells induced by H2O2, promote cell proliferation, and reduce cell apoptosis. Mogrosides may exert antioxidant effects by activating the SIRT1/Nrf2 signaling pathway.