Obesity has become a global concern because of increasing the risk of many diseases. Alterations in human gut microbiota have been proven to be associated with obesity, yet the mechanism of how the microbiota are altered by high salt diet (HSD) remains obscure. In this study, the changes of Small Intestinal Microbiota (SIM) in obesity-T2DM mice were investigated. High-throughput sequencing was applied for the jejunum microbiota analysis. Results revealed that high salt intake (HS) could suppress the body weight (B.W.) in some extent. In addition, significant T2DM pathological features were revealed in high salt-high food diet (HS-HFD) group, despite of relatively lower food intake. High-throughput sequencing analysis indicated that the F/B ratio in HS intake groups increased significantly (P < 0.001), whereas beneficial bacteria, such as lactic acid or short chain fatty acid producing bacteria, were significantly decreased in HS-HFD group (P < 0.01 or P < 0.05). Furthermore, Halorubrum luteum were observed in small intestine for the first time. Above results preliminary suggested that in obesity-T2DM mice, high dietary salt could aggravate the imbalance of composition of SIM to unhealthy direction., (© 2023. The Author(s).)