Abstract: To investigate the effect and possible mechanisms of triterpenic acid-enriched fraction from Cyclocarya paliurus(TAE)on glucagon secretion in insulin-resistance pancreatic α cells, the model of insulin resistance in αTC1-6 cells was induced by long term exposure to high glucose. Experimental groups were divided as follow: control(5. 5 mmol/L glucose), model(25 mmol/L), TAE(1, 5, 10 μg/mL), and TAE(10 μg/mL)plus wortmannin(10 nmol/L)group. The supernatant and lysate of treated cells were collected to determine glucagon secretion by ELISA kit. The mRNA and protein abundance of IRS-1, PI3K and Akt were measured by qPCR and Western blot analysis. Results showed that TAE could not only significantly reduce glucagon secretion induce by high glucose in a dose-dependent manner, but also remarkably increased the mRNA and protein abundance of IRS-1, PI3K and Akt in αTC1-6 cells. However, these effects of TAE were reversed by PI3K inhibitor wortmannin. In conclusion, it suggested that TAE could improve the insulin resistance induced by high glucose in pancreatic α cells which may be related with the activation of IRS-1/PI3K/Akt signaling pathway.