By establishing insulin resistance model of Caenorhabditis elegans, the effects of Rhodiola rosea extract and its compounds on glucose level, insulin signal intensity, antioxidant enzymes and cell apoptosis of C. elegans were investigated in present study. The mRNA expression of DAF-2, DAF-16, AkT-1, SKN-1, AAK-2 and SOD-3 were detected by qRT-PCR. The results revealed that R. rosea extract contain salidroside, kaempferol, chlorogenic acid, kaemphenol-7-O-glucoside, caffeic acid, and quercetin, etc. At the concentration of 200 μg/mL, R. rosea extract treated C. elegans showed increased insulin signal intensity by 52.46% compared with the normal group, while, glucose content decreased by 72.13% and reactive oxygen species (ROS) level decreased by 36.84%. Compared with high glucose model group, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) increased by 10.9, 14.2 and 27.9, respectively. After R. rosea extract intervention, the expression levels of DAF-2, AkT-1, AAK-2, SKN-1 and other genes significantly increased. These results also indicated that R. rosea extract could activate insulin receptor substrate (IRS) and adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) pathways to enhance insulin signaling, promote nutrient metabolism, and achieve the effect for improving insulin resistance of C. elegans.