Objective: To investigate the mechanism of centella asiatica alcohol extract on hepatic insulin resistance of Zucker diabetes fatty(ZDF) rats. Method: Six male (fa/+) ZDF rats were selected as control group

and 18 modeled male (fa/fa) ZDF rats were randomly divided into three groups

namely model group (normal saline 10 ml·kg-1)

metformin group (0.18 g·kg-1·d-1) and centella asiatica group (0.1 g·kg-1·d-1) based on body weight and random blood glucose. Body weight

random blood glucose and fasting blood glucose were monitored every two weeks. Materials were collected six weeks later to measure the fasting blood glucose (FBG) and fasting serum insulin

and calculate insulin resistance index homeostasis model of assessment for insulin resistance index (HOMA-IR). Gene expressions of insulin receptor substrate 2 (IRS2)

3-phosphoinositide-dependent protein kinase 1 (PDK1) and glucose transporter 2 (GLUT2) in the liver were detected by Real-time polymerase chain reaction (Real-time PCR). Protein expressions of PDK1 and IRS2 were observed by immuno-histochemical method. Result: The administration groups could significantly improve weight

random blood glucose

fasting blood glucose

fasting serum insulin and insulin resistance index of (fa/fa) ZDF rats (P<0.01). Compared with model group

IRS2

PDK1 and GLUT2 mRNA expressions and PDK1 and IRS2 protein expressions of centella asiatica group increased (P<0.01). Conclusion: Centella asiatica alcohol extract can effectively improve the hepatic insulin resistance of (fa/fa) ZDF rats. Its mechanism may be related to expressions of IRS2

PDK1 in insulin signaling pathway and glucose transporter GLUT2.