Both human and animal studies show differences by sex in the effects of endogenous sex hormones on insulin resistance. In men, low plasma testosterone is associated with obesity, upper body fat distribution, and increased levels of glucose and insulin, whereas hyperandrogenicity is associated with an increased risk for type 2 diabetes and cardiovascular disease in women. Most of these studies were cross-sectional. Sex hormone binding globulin (SHBG) is an indirect measure of androgenicity, because its concentration is mainly determined by free estrogen and testosterone. Several prospective studies show that low levels of testosterone and SHBG predict the development of type 2 diabetes in middle aged and elderly men. Low levels of SHBG alone did not significantly predict incident type 2 diabetes in middle aged men; in contrast, low levels of SHBG alone predicted the development of type 2 diabetes in women. Insulin is known to regulate SHBG production by the liver. Low circulating SHBG concentrations are known to occur in adults as a consequence of hyperinsulinaemia/insulin resistance. Tumor necrosis factor alpha (TNF-alpha) might contribute to the development of insulin resistance in glucose intolerant subjects. Impaired glucose tolerance is a risk category for type 2 diabetes. An increase in circulating TNF-alpha is associated with peripheral insulin resistance and increased plasma glucose and insulin levels prior to the onset of type 2 diabetes mellitus. TNF-alpha is also sex dependent and increased levels of this cytokine occurs in male type 2 diabetic patients. The term insulin resistance refers to an impaired biological response to either exogenous or endogenous insulin. The fasting glucose/ insulin ratio is a useful screening test for insulin resistance and setting a value of less than 7 as abnormal, indicating insulin resistance. Our study was conducted on 20 healthy subjects as a control group, beside 61 type 2 diabetic patients including 30 controlled diabetics and 31 uncontrolled diabetics. We measured serum levels of Fasting glucose, TNF-alpha, SHBG, insulin, glycosylated Hb, ALT and AST. The results revealed: 1-that in the group of 61 controlled and uncontrolled type 2 diabetic patients, SHBG, TNF-alpha and Glucose/insulin ratio are significantly increased compared to the control healthy group. However, only SHBG and Glucose/insulin ratio are significantly increased in the uncontrolled group compared to the controlled group, which means that SHBG and G/I ratio are affected by the glycemic state in patients with type 2 diabetes mellitus. TNF-alpha showed no significant increase whether the diabetic patient belongs to the controlled or uncontrolled group, and this means that the level of TNF-alpha is independent of the control of the glycemic state in patients with type 2 diabetes mellitus. 2- That TNF-alpha is a better marker for insulin resistance in type 2 diabetes mellitus of the three parameters: SHBG, TNF-alpha or fasting glucose/insulin ratio.