Diabetes mellitus is one of the most common non-communicable diseases of the current era. The burden of this disease is immense owing to transition in lifestyle and dietary habits, ageing of the population and urbanization in the setting of a genetically predisposed environment. Aim of the Work: The aim of current study was to study the plasma netrin 1 level in type II diabetes mellitus patients with and without proteinuria to elucidate the role of netrin-1 in the pathogenesis of type 2 diabetes and expand its potential for diagnosis. A case control study was conducted on (54) subjects including 26 male and 28 female they were classified into 2 groups as follows: Patient group: include 34 patients with type 2 diabetes mellitus based on Hb A1c 6.5 % according to ADA 2020 diagnostic criteria for diabetes. Control group: include 20 age and sex matched healthy control subjects. Patients were subdivided into 2 subgroups: Subgroup(A): includes 17 patients with type 2 diabetes mellitus without proteinuria. Subgroup(B): includes 17 patients with type 2 diabetes mellitus with proteinuria. This study showed that there was a high statistically significant increase in serum netrin 1 in patient group compared to control group. The study revealed no statistically significant correlation between serum netrin 1 and other studied parameters in patient group. Our study revealed that there was a high statistically significant increase in serum ALT, AST and albumin creatinine ratio in patient group than control group, also, there was a high statistically significant increase in lipid profile including serum cholesterol, triglycerides and LDL in patient group than control group & a high significant decrease in HDL in patient group than control group.  The study showed that there was a high statistically significant increase in fasting blood sugar (FBS), 2 hours post prandial blood sugar (2hppbs), HbA1C, fasting insulin & HOMA IR in patient group than control group. This study showed that, there was a statistically significant increase in disease duration in subgroup B compared to subgroup A. There was a high statistically significant increase in serum netrin 1 in subgroup B than other studied groups. There was a non -significant increase in serum netrin 1 in subgroup B compared to subgroup A, a high significant increase in serum netrin 1 in subgroup A compared to control group and a high significant increase in serum netrin 1 in subgroup B in comparison to control group. Conclusion: From the results of the current study, we concluded that plasma level of Netrin 1 is significantly higher in patients with type 2 diabetes mellitus than control group, there was a non-significant increase of serum netrin 1 in diabetic patients with proteinuria in comparison to type 2 DM patients without proteinuria. This could focus the light on the importance of Netrin 1 on the pathogenesis of nephropathy in diabetes.