Conditions of hypoandrogenism in men have been linked to insulin resistance, suggesting that alterations in normal sex steroid physiology could play a role in the pathogenesis of Type 2 diabetes mellitus (T2DM). Sex hormone-binding globulin (SHBG) gene polymorphisms may be the cause of sex steroid alteration. The aim of this work is to study the effect of SHBG gene polymorphisms on the risk of T2DM through its impact on testosterone and oestradiol level in Egyptian men.A case control study was performed in the diabetes clinic at Zagazig University Hospital on 185 males with Type 2 diabetes and their matched healthy controls. Two polymorphisms (rs6257 and rs6259) of the gene encoding SHBG were genotyped and serum levels of SHBG, testosterone and oestradiol were measured by enzyme-linked immunosorbent assay (ELISA).Carriers of rs6257 variant allele (CC or CT) and carriers of rs6259 wild allele (GG) appear to have a high risk of diabetes than carriers of other alleles (OR 2.241, 1.585 and 2.391, respectively). They also showed a significant decrease in plasma level of both SHBG and testosterone and a significant increase in oestradiol blood level compared with carriers of other alleles.Sex hormone-binding globulin gene polymorphisms at position rs6257 and rs6259 are associated with higher risk of T2DM in Egyptian men, through lowering circulating levels of SHBG and consequently, lowering testosterone and elevating oestradiol level.