To explore the effects and mechanisms of Yixiao Formula on diabetes combined with fatty liver.Methods:Twelve-week-old male spontaneous diabetic(KKAy) mice were randomly divided into a model group,a Chinese medicine(Yixiao Formula) intervention group,and a Western medicine(losartan) intervention group using a random number table.The control group consisted of age-matched male inbred(C57BL/6J) mice.The intervention period lasted 12 weeks.Changes in blood glucose,blood lipids,and liver function were observed before and after the intervention.Liver tissue was pathologically stained,and changes in proteins and mRNAs in transforming growth factor-β1(TGF-β1) signaling pathway in liver tissues were detected.Results:Compared to the model group,the Yixiao Formula group showed a significant reduction in body weight and liver index after 8 weeks of intervention(P<0.05,P<0.01).Fasting blood glucose levels significantly decreased at 4,8,and 12 weeks of intervention(P<0.01).After 8 weeks of intervention,cholesterol,triglycerides,low-density lipoprotein cholesterol,and alanine aminotransferase levels were reduced(P<0.05,P<0.01).Pathologically,the steatosis score decreased after 4 weeks of Yixiao Formula intervention(P<0.05).After 12 weeks of intervention,the protein and mRNA expression of TGF-β1 was significantly downregulated(P<0.05,P<0.01).Conclusion:Yixiao Formula can significantly improve obesity and glucose-lipid metabolism disorders in KKAy mice,regulate protein and gene expression in TGF-β1 signaling pathway,and reduce liver steatosis.