AIM To investigate the effects of an extraction of Rhodiola crenulata (ERC) on type 2 diabetes mellitus (T2DM) by impmving insulin resistance.METHODS The spontaneous T2DM model KKAy mice were treated with ERC.The glucose tolerance was estimated by oral glucose tolerance tests (OGTT).The insulin resistance was evaluated by insulin tolerance tests (ITT), the glucose infusion rate (GIR) in hyperinsulinemic-euglycemic clamp tests, the whole-body insulin sensitivity index (ISWBI), the serum insulin level, and the homeostasis model assessment of insulin resistance (HOMA-IR), respectively.The hepatic protein expressions were estimated by western blotting.The recombinant human protein tyrosine phosphatase 1B (PTP1 B) was prepared and used for the measurement of PTP1B activity in vitro.RESULTS The hyperglycemia and glucose intolerance in KKAy mice were improved significantly by the administration of ERC (200 mg· kg-1) orally.In the ERC-treated mice, the changes of blood glucose after the insulin loading in ITT were enhanced and its AUC value was reduced by 32.8% ; the level of GIR was increased by 2.8 folds; the value of ISWBI was enhanced by l.7 folds; the levels of serum insulin and HOMA-IR were decreased by 19.1% and 31.5%, respectively,compared with those in KKAy model control mice.The effects of ERC on insulin resistance was associated with insulin signaling pathway, especially, showed strongly inhibition on PTP1B activity with EC50 of 1.161 mg·L-1 in vitro and on PTP1B expression in the liver of KKAy mice by 30.0% decrease in vivo.CONCLUSION Targeting on PTP1 B, ERC can treat T2DM by improving insulin resistance in KKAy mice.