Abstract: The objective of this work was to explore the effect of D-chiro-inosiol (DCI) on lifespan of Caenorhabditis elegans influenced by the glucose-induced oxidative damage and underlying mechanism of anti-aging. Methods:The C. elegans were fed in high-glucose NGM medium with DCI at final concentrations of 0, 5, 10, 20 μm/L. The impacts of DCI on lifespan were observed by counting method. The fluorescence intensity of lipofuscin and reactive oxygen species (ROS) level in vivo was detected. The activities of antioxidant enzyme were determined by superoxide dismutase (SOD) and catalase (CAT) commercial kits. The expression of age-related genes was detected with real-time polymerase chain reaction (real-time PCR). Results:After being fed with different doses of DCI, C. elegans exhibited a longer average lifespan than those in the model group (10、20 μm/L, p<0.05). The levels of lipofuscin's autofluorescence and ROS in C. elegans were significantly reduced after 20 μm/L DCI supplementation (p<0.01). The SOD and CAT activities were increased significantly after 20 μm/L DCI supplementations (p<0.05). The mRNA expression levels of daf-2 and age-1 decreased significantly while sir-2.1, sod-3, daf-16, and ctl-1 mRNA expression showed an increasing trend after 20 μm/L DCI supplementations (p<0.05). Conclusion:DCI may play a positive and protective role on glucose-induced oxidative damage in C. elegans.Simultaneously, the anti-aging activity of DCI may be accompanied by regulating the expression levels of anti-aging genes.