[ ABSTRACT] AIM:To study the role of Radix Pseudostellariae polysaccharide ( RPP) in hepatic insulin resist-ance.METHODS:Six-week-old C57BL/6J mice were randomly divided into low-fat diet (LFD) control group and high-fat diet ( HFD) model group.After 16 weeks, intraperitoneal pyruvate tolerance test ( IPPTT) was performed to determine the establishment of the HFD-induced hepatic insulin resistance model.HFD containing RPP (500 mg/kg) was given for 4 consecutive weeks.IPPTT, liver malondialdehyde ( MDA) level and liver mitochondrial MDA level were measured.The protein levels of p-AKT (Ser473/Thr308), p-AMPK, nuclear factor E2-related factor 2 (Nrf2), NQO1 and IκBαin the liver tissues were measured by Western blot.RESULTS:After administration of RPP, a significant reduction in the levels of blood glucose and hepatic mitochondrial MDA was observed.The levels of p-AKT ( Ser473/Thr308) and p-AMPK were significantly elevated in the liver tissues.The hepatic IκBαlevels were up-regulated.RPP also enhanced the expression of Nrf2 system-regulated proteins NQO1 and HO-1 in the liver tissues.CONCLUSION:Radix Pseudostellariae polysaccha-rides effectively reduce HFD-induced hepatic insulin resistance in C57BL/6J mice and improves liver glucose metabolism by ameliorating HFD-impaired hepatic transduction of insulin signaling, activating Nrf2-associated signaling and inhibiting the expression of inflammatory signaling proteins.