Objective:To investigate the effect of Liuwei Dihuang Pill on glucose metabolism in insulin-resistant mice and its relationship with osteocalcin. MethodsMice with insulin resistance induced by high-fat diet were divided into low-, middle- and high-dose groups of Liuwei Dihuang Pill, Western medicine group (pioglitazone), model group and normal group. After 8 weeks of intervention, fasting blood glucose (FBG), fasting insulin (Fins) and osteocalcin were detected.  Results:Compared with the model group, FBG was improved significantly in insulin-resistant mice in the low-dose group (P<0.01); Fins was significantly lower in the low- and high-dose groups of Liuwei Dihuang Pill (P<0.01, P<0.05); uncarboxylated osteocalcin was increased significantly in insulin-resistant mice in the groups of Liuwei Dihuang Pill (P<0.01, P<0.05) and the ratio of uncarboxylated to carboxylated osteocalcin increased significantly in the low-dose group of Liuwei Dihuang Pill. Correlation analysis showed a negative correlation between uncarboxylated osteocalcin and FBG (P<0.05); the ratio of uncarboxylated to carboxylated osteocalcin was negatively correlated with FBG (P<0.01) and Fins (P<0.05).  Conclusion:FBG and Fins are significantly improved in insulin-resistant mice in the low-dose group of Liuwei Dihuang Pill. Compared with uncarboxylated osteocalcin, the ratio of uncarboxylated to carboxylated osteocalcin better explains the improvement of glucose metabolism by Liuwei Dihuang Pill.