Abstract.Retinal pigmented epithelial cell (RPE) oxidative stress is known to have a vital role in the etiology of age-related macular degeneration (AMD). The present study aimed to investigate whether allicin, a natural product with antioxidant activity, was able to protect RPEs (ARPE-19) from hydrogen peroxide (H 2 O 2 )-induced damage, and to determine the underlying mechanisms. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to determine cellular viability, and reactive oxygen species (ROS) were detected using a ROS Assay kit. The results demonstrated that allicin was able to protect ARPE-19 cells from H 2 O 2 -induced damage in a dose-dependent manner. In addition, allicin attenuated oxidative stress by reducing the levels of intracellular ROS and malondialdehyde (MDA), and enhancing the glutathione/glutathione disulfide (GSSG) ratio. With regards to the underlying mechanism, allicin was able to markedly modulate the expression levels of ROS-associated enzymes, including superoxide dismutase, NADPH oxidase 4 and NAD(P)H dehydrogenase quinone 1, and elevate the activity of nuclear factor erythroid 2-related factor 2 in the H 2 O 2 -stimulated ARPE-19 cells. These results suggested that allicin may exert protective effects against H 2 O 2 -induced cytotoxicity in RPEs via ROS regulation.