Hyperglycemia is a known cause of inflammation (1,2) followed by increased production of acute phase proteins and pro-inflammatory cytokines, including TNF-α.(1-3) Monocytes taken from diabetic patients produce higher levels of TNF-α in comparison with control monocytes taken from healthy subjects.(4) On the other hand, TNF- α is a known cause of hyperglycemia secondary to insulin resistance. Hypoglycemia was reported as one of the complications of treatment with TNF-α inhibitors.(5) This study was conducted to evaluate plasma TNF-α in obese diabetic patients and to determine its relation to glycemic control. A random sample of 40 obese type II diabetic patients (cases) and 40 obese non-diabetic subjects (controls) were interviewed and examined clinically to exclude presence of acute or chronic medical illness. The two groups were matched according to age, sex, body mass index and area of residence. Hemoglobin A1c was measured for each participant using the “NycoCard Hemoglobin A1c test” (Axis -Shield/ Norway). Fasting blood sugar was measured using one touch® glucometer (LifeScan Canada Ltd). Plasma TNF-α was measured using commercially available ELISA kits from ADIPO Bioscience/ USA. The research conforms to the ethical principles of medical research developed by the World Medical Association Declaration of Helsinki. The chi square test was used to test distribution of categorical variables. The difference in mean between the test and the control groups was assessed with the independent student’s t test. The majority of obese diabetic patients had high plasma TNF-α values (≥ 5pg/ml) with “mean ± SEM” = “11.09 ± 3.03” whereas the majority of obese non-diabetic subjects had lower values with “mean ± SEM” = “4.68 ± 2.31”; P= 0.003. More than half (58%) of those with high TNF-α values had abnormal hemoglobin A1c (≥ 6.5%, P= 0.037). The relation between plasma TNF-α and fasting blood sugar in all participants was statistically insignificant (P= 0.515). These data suggest that the higher plasma TNF-α in obese diabetic patients compared to the non-diabetics cannot be explained by obesity alone since both groups were obese. A significant relation was found between high plasma TNF-α and poorly controlled diabetes mellitus, indicating that hyperglycemia might be responsible for the rise in TNF-α. The relation between plasma TNF-α and fasting blood sugar was statistically insignificant. This indicates that TNF-α production is most probably associated with a long term, rather than a short term effect of hyperglycemia.