To investigate the effect of Baihu Decoction with Ginseng on AMP-activated protein kinase/sterol regulatory element-binding protein-1(AMPK/SREBP1) signaling pathway in type 2 diabetes mellitus(T2DM) model rats.Methods:T2DM model rats were established using high-fat feed combined with streptozotocin(STZ) injection，followed by intragastrically administrating different doses of Baihu Decoction with Ginseng.The therapeutic effect of Baihu Decoction with Ginseng on T2DM model rats was evaluated by detecting the relevant serum biochemical indices and liver histopathological changes after intragastrical administration in each group of rats; Then，after the Baihu Decoction with Ginseng intervention was detected by qPCR and Western blot method，the genes and protein levels of key factors AMPLK/SREBP1 signaling pathway，such as AMPK，acetyl-coenzyme A carboxylase 1(ACC1)，fatty acid synthase(FASN)，and ATP citrate lyase(ACLY) were detected in the liver tissues of rats in each group，and the mechanism of action of Baihu Decoction with Ginseng in the treatment of T2DM model rats was preliminarily explored.Results:Baihu Decoction with Ginseng significantly reduced the levels of fasting blood glucose(FBG)，oral glucose tolerance test(OGTT)，glutamate-pyruvate transaminase(GPT)，glutamic-oxaloacetic transaminase(GOT)，total cholesterol(TC)，triglycerides(TG) and low-density lipoprotein cholesterol(LDL-C) in the serum of T2DM models，and increased the levels of high-density lipoprotein cholesterol(HDL-C).It also improved liver histopathological changes in the liver of T2DM model rats.The qPCR and Western blot results showed that Baihu Decoction with Ginseng could significantly reduce the levels of AMPK gene and protein levels in the liver tissue of T2DM model rats，and upregulate the genes and proteins levels of SREBP1，ACC1，ACLY，FASN.Conclusion:Baihu Decoction with Ginseng has a therapeutic effect on T2DM model rats，possibly by modulating the AMPK/SREBP1 signaling pathway in liver tissue and improving lipid metabolism.