Background: Diabetic kidney disease (DKD) has become the leading cause of the end-stage renal disease (ESRD) and it is one of the most devastating complications of type 2 diabetes mellitus (T2DM). Its pathogenesis encompasses multiple dysregulated epigenetic mechanisms. Long non-coding RNAs (lncRNAs) have an important function in various diseases. However, their roles in DKD remain mainly unknown. Objective: The present study was performed to explore the relative expression level of lncRNA taurine upregulated gene 1 (lncRNA Tug1) in Egyptian patients with T2DM and CKD and to investigate its associations with the progression of CKD. Patients and methods: This cross-sectional-controlled study included a total of 50 patients with T2DM and 50 age and sex-matched controls, attending at Internal Medicine, Faculty of Medicine, Zagazig University Hospitals. Quantitative real-time reverse-transcription PCR (qRT-PCR) was used to detect the expression levels of lncRNA TUG1 Results: patients with T2DM had statistically significantly lower values of the relative expression level of lncRNA Tug1 compared to the control group (1.313±0.72, vs 2.354±0.97, P ˂0.001). Interestingly, patients with macroalbuminuria (0.48±0.311) had statistically significant lower values of the relative expression level of lncRNA Tug1compared to patients with microalbuminuria (1.42±0.49) and patients with normoalbuminuric (1.86±0.636), P ˂0.01. In patients with DKD among studied variables, serum creatinine and UACR were the main independent parameters associated with the relative expression of lncRNA Tug1. Conclusion: It could be concluded that circulatory lncRNA Tug1 expression level is downregulated in patients with T2DM in a particular patient with macroalbuminuria. Thus, circulatory lncRNA Tug1 relative expression level may have a reno-protective role.