Background: Diabetic nephropathy (DN) is one of the chronic complications of diabetes mellitus (DM) that cause a common end-stage renal disease (ESRD). Cytokines regulate inflammatory processes in response to the degree of inflammations. Overproduction of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNF-α) and interlukin-6 (IL-6) play a role in the development and progression of DN. Aim: To evaluate the levels of TNF-α and IL-6, and their implication in diagnosis and progression of nephropathy in patients with type 2diabetes mellitus (T2DM). Subjects and Methods: Sixty subjects (45 patients, 15 normal) were selected from Suez city and general hospital in Suez, with mean age43.3±8.2years. They were classified into four groups, Group I:healthy subjects, Group II:T2DMpatients; GroupIII: Nephropathicpatients identified by high level of creatinine in blood and microalbuminurea; and Group IV: Nephropathic patients with T2DM as identified by high level of creatinine and glucose in blood and microalbuminurea. Blood and urine samples were collected and tested for fasting and postprandial blood glucose (PBG) level, glycosylated hemoglobin (HbA1C), liver and kidney function tests. In addition, serum TNF-α, and IL-6levels were measured by Enzyme Linked Immune Sorbent Assay (ELISA). Results: The level of IL-6 was significantly increased (p<0.05) in nephropathy and DN groups compared to control and T2DM groups with a significant positive correlation between its level and the duration of diabetes in DN group and significant negative correlation between its level and duration of diabetes in T2DM group. On the other side, TNF-α levels were significantly decreased(p<0.05) in both nephropathy and DN groups compared with control and T2DM groups which was not correlate to the duration of diabetes in either T2DM or DN groups. Conclusion: Tracking the levels of IL-6 cytokine in T2DM patients could be used as a marker for progression to DN patients.