Purpose: This study aimed to examine the effects of Empagliflozin on the mice model of HFD/STZ-induced T2DM and liver fibrosis, and the correlations with gut microbiota. Methods: The HFD/STZ-induced T2DM and liver fibrosis mice were treated with Empagliflozin for 6 weeks. After the intervention, OGTT and IPGTT were performed to assess glucose tolerance and insulin resistance in mice. The histological chemistry and indicators of liver pathology and liver fibrosis were assessed. Moreover, 16S rRNA amplicon sequencing for gut microbiota was performed to explore the changes of gut bacterial composition. And we analyzed the correlation between alterations in intestinal microbial composition and liver fibrosis score or glucose metabolic indicators. Results: 6-week Empagliflozin intervention improved glucose metabolism, and attenuated liver fibrosis in HFD/STZ-induced mice, which might be related to the alterations of gut microbiota. Furthermore, the abundance of Lactobacillus was increased, while Ruminococcus and Adlercreutzia were reduced in Empagliflozin-treated mice, which were positively associated with liver fibrosis and glucose metabolism in correlation analysis. Conclusion: Empagliflozin ameliorated glucose metabolic dysfunction and liver fibrosis in HFD/STZ-induced mice, whose effects might be due to the beneficial balance of gut microbiota composition. Our study provided evidence and highlighted improvement of gut-liver axis by inhibition of SGLT2 in T2DM and liver fibrosis.