Abstract:s A variety of chronic diseases are attributed to oxidative stress induced by imbalance of free radical reaction. Spirulina polysaccharides(PSPs) are natural active substances with strong antioxidant, but its mechanisms of antioxidant and anti-aging are still unclear. In the current study, the antioxidant activity of PSPs in vitro was determined by chemical methods, and the resistance of PSPs to oxidative stress of Caenorhabditis elegans (C. elegans) was tested in vivo. The results showed that PSPs had DPPH· scavenging capacity and total reducing power promoting capacity, which was dose-dependent. PSPs prolonged the life span of C. elegans in a dose-dependent manner. The antioxidant capacity was enhanced by improving the exercise abilities and the activities of antioxidant enzymes SOD and CAT, reducing the accumulation of senescence pigment and the level of intracellular reactive oxygen species (ROS). Under the oxidative stress of 1‰ H2O2, PSPs significantly prolonged the life span of C. elegans. The qRT-PCR results indicated that PSPs could significantly up-regulate the mRNA expression of daf-16, skn-1, and sir-2.1 genes. These results suggested that PSPs could enhance the resistance to oxidative stress and prolong the life span of C. elegans by increasing the activity of antioxidant enzymes and the expression of related genes through the insulin signaling pathway.