In muscle cells, there are two important signal pathways to regulate glucose transport and metabolism, the insulin signaling pathway and AMPK pathway. Insulin signaling is mediated by cascades of phosphorylation/dephosphorylation events. Insulin signal transduction in skeletal muscle is mediated by a series of phosphorylation cascades linking initial activation of the insulin receptor, a tyrosine kinase receptor, to downstream substrates. Extensive studies have indicated that the ability of the receptor to autophosphorylate and phosphorylate intracellular substrates is essential for its mediation of the complex cellular responses to insulin. IR plays an important role in the regulation of whole body metabolism and pathogenesis of diabetes. In the present study, we evaluated the mRNA expression of IR by quantitative R428 RT-PCR analysis and the protein level of p-IR by ELISA assay, respectively. As we supposed, the mRNA and protein levels of IR in OM and OM2 treated groups dramatically increased compared to that in control group, contributing to the improved insulin sensitivity. Activated IR transduces the insulin signal by activating PI3K/ Akt pathway to promote glucose uptake. Current research seeks to ameliorate insulin resistance by finding ways to increase PI3K/Akt activity and restore insulin sensitivity. Activated Akt phosphorylates and regulates the activities of many downstream proteins involved in multiple aspects of cellular physiology. Here, ELISA results of p-PI3K and p-Akt indicated that the oligomannuronate and its chromium complexes stimulated the activation of proteins in the PI3K/Akt signaling pathway, to an extent similar with insulin, and had an effect on glucose uptake. The PI3K/Akt pathway has been demonstrated to be able to regulate GLUT4 translocation. The importance of GLUT4 in glucose homeostasis has been studied extensively in recent years. GLUT4-mediated glucose transport in muscle is essential to the maintenance of glucose homeostasis. Results indicated that the mRNA expression of GLUT4 increased in C2C12 cells after oligosaccharides treatments. Moreover, the increased production of GLUT4 might directly enhance the insulin stimulated glucose uptake. So the oligomannuronate and its chromium complexes might be able to upregulate the insulin signaling to promote glucose transport through the PI3K/Akt pathway after internalization. AMPK is considered a promising drug target for type 2 diabetes. Activation of the enzyme in the liver or skeletal muscle with the cell-permanent AMP analog AICAR is associated with diminished gluconeogenesis and enhanced glucose uptake, respectively. In skeletal muscle, AMPK activation may be involved in the effects of repeated exercise to improve insulinsensitive glucose uptake, because of its ability to increase expression of GLUT4 and perhaps other effects. In this study, by assessing the phosphorylation state of AMPK using western blot and ELISA assay.