The present study aimed to explore the effect of an anti-inflammatory RG-II type polysaccharide (KMPS) purified from Aconitum coreanum (Le'vl.) on glucose metabolism in high-fat diet-induced obese (DIO) mice. Treatment with KMPS for 4 weeks significantly reduced the fasting blood glucose, increased the sensitivity to insulin and improved glucose tolerance. Concurrently, KMPS supplementation also markedly inhibited inflammatory cytokine expression in serum and insulin target tissues and decreased the proportion of M1-type macrophages in adipose tissue, which was considered as the potential hypoglycaemic mechanism. In mechanism study, it was found that KMPS reduced the serine phosphorylation of IRS-1 by inhibiting the activation of the NF-κB pathway, thereby restoring the utilization of glucose by the PI3K/AKT pathway. These results suggested that KMPS may be a potential component for targeting inflammation in the treatment of type 2 diabetes.