In the present study we measured interleukin-18 (IL-18) and tumour necrosis factor-alpha (TNF-alpha) levels by enzyme linked immunosorbent assay (ELISA) in sera from 65 diabetic [30 with type 1 insulin dependent diabetes mellitus (IDDM) and 35 with type 2 non-insulin dependent diabetes mellitus (NIDDM)] patients and 15 healthy volunteers, to investigate their associations with metabolic parameters and to elucidate their roles in the pathogenesis of diabetic complications especially diabetic nephropathy. Levels of IL-18 and TNF-alpha were significantly higher in both IDDM and NIDDM individuals as compared to the control group. Similarly, their levels in patients with diabetic nephropathy increased gradually according to the clinical stage of the disease, being highest in macroalbuminuric stage. Correlation analyses showed that the serum IL-18 and TNF-alpha concentration were positively correlated with each other and positively with fasting plasma glucose (FPG), 2h postprandial glucose, glycosylated hemoglobin (HbA1c), triglyceride, and urinary albumin levels and negative correlation between TNF-alpha and high density lipoprotein cholesterol (HDL-C) were also found in diabetic subjects. High serum levels of IL-18 and TNF-alpha suggested that they might play a role in the pathogenesis of DM and in the development of nephropathy in diabetic patients whether of type 1 or 2.