Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae),Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae),the three major herbs of JinQi-JiangTang tablet,a traditional Chinese medicine (TCM) formula.The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKAy mice and insulin-resistant L6 myotubes.To investigate the mechanisms by which JQ-R improves insulin sensitivity,a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes.Glucose uptake and expression of factors involved in insulin signaling,stress,and inflammatory pathways were detected by immunoblotting.JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKAy mice.JQ-R also improved the plasma lipid profiles.JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells,and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT.The phosphorylation levels of nuclear factor kappa B (NF-κB p65),inhibitor of NF-κB (IκB α),c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group.Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKAy mice.JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress.JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.