Dry age-related macular degeneration (AMD), a major cause of blindness in aged population, is related to oxidative stress induced damage of the retinal pigmented epithelial (RPE) cells, without efficient medicine. We have previously found out that artemisinin, a famous drug from Chinese traditional medicine, was involved in different kinds of biological activities including antioxidant function. However, it remains unclear whether artemisinin can prevent or reverse AMD by suppressing oxidative stress of RPE. To preliminary address this question, we detected the protective effect of artemisinin on PRE cell line D407 against H2O2-induced oxidative stress, and further investigated the mechanism related to AMPK pathway. Our results showed that artemisinin reduced intracellular ROS generation and oxidative stress, decreased LDH release and promoted the survival ratio in D407 cells treated with H2O2. Western blotting showed that artemisinin stimulated the phosphorylation of AMP-activated protein kinase (AMPK) in a concentration and time dependent manner. On the other hand, AMPK inhibitor Compound C or knock-down of AMPK by siRNA was able to partly reverse the protective effect of artemisinin in D407 cell line. More importantly, artemisinin worked as well in primary cultured retinal pigment cells which was blocked by inhibitors of AMPK similarly. Taken together, artemisinin could prevent human retinal pigment cells from H2O2-induced oxidative damage at least partly by enhancing the activation of AMPK. Therefore, artemisinin may be a potential candidate for treatment of the age-related disease, retinal disorders like AMD.