Background: Diabetes mellitus (DM) is the world's most common cause of chronic kidney diseases (CKD), with approximately 1 in 4 adults with DM having CKD and 1 out of 10 to 20% of DM patients die from CKD. Objective: The current study aims to investigate the correlation between Notch-2 and Jag-1expressions and specific inflammation biomarkers IL-1β and IL-6 with different stages of diabetic nephropathy. Methods: From August 2018 to January 2019, three hundred subjects were recruited for this study. One hundred and fifty subjects were healthy and age-matched to the diabetic group and selected as a control group. Another 150 patients with an established diagnosis of type 2 diabetes (T2DM) according to the criteria of the American Diabetes Association (ADA) were also recruited. Blood specimens were eventually used to identify the expressions Notch-2 and Jagged-1 and the levels of inflammatory biomarkers IL-1β and IL-6. Result: The current study shows a significant increase in gene expression and inflammatory biomarkers in patients with moderate and severe diabetic nephropathy compared to the control group. However, there was no significant difference between healthy control and mild diabetic nephropathy patients. This study shows a close association between the increase in the levels of inflammatory biomarkers IL-1β and IL-6 as well as the gene expressions levels of both Notch-2 and Jag-1 with human diabetic nephropathy. Conclusion: According to our findings, we emphasize the use of Notch-2 and Jag-1 expressions and IL-1β and IL-6 levels as potential biomarkers for different stages of diabetic nephropathy. © 2021 Wajdy J. Al-Awaida, Wasan S. Hameed, Haider J. Al Hassany, Moh’dMohanad Al-Dabet, Omar Al bawareed, Najah R. Hadi.