O-6-methylguanine which is formed in cellular DNA by alkylating agents is a toxic and mutagenic lesion. O-6-methylguanine is repaired by DNA repair protein, O-6-methylguanine DNA methyltransferase. Deficient repair of O-6-methylguanine has been suggested to be a contributory factor in the etiology of some diseases. Streptozotocin (SZ) is an alkylating compound that is often used to induce diabetes in experimental animals. We aimed to determine O-6-methylguanine DNA methyltransferase level in pancreas of SZ-induced diabetic rats. Serum levels of glucose and fructosamine, and pancreatic O-6-methylguanine DNA methyltransferase level were measured in the streptozotocin-induced diabetic and control rats. Serum glucose and fructosamine levels were found to be higher in the diabetic group than those in the control group (P<0.001 and P<0.001, respectively). Pancreatic O-6-methylguanine DNA methyltransferase level was lower in the diabetic group (68.06+/-12.37 fmol/mg protein) than in the control group (89.45+/-13.83 fmol/mg protein), (P<0.01) and there was a negative correlation between serum fructosamine level and pancreatic O-6-methylguanine DNA methyltransferase level (r: -0.6, P<0.02). These data imply that O-6-methylguanine DNA methyltransferase depletion may be one of the mechanisms for diabetogenic action of SZ in rats.