The use of nanoparticles in medicine is an attractive proposition. In the present study, the protective effect of zinc oxide nanoparticles (ZnONPs), on oxidative stress in experimental - induced diabetes in rats were evaluated. One hundred and sixty male albino rats with weight 130 ± 30 and age 12-16 weeks were used. Animals were grouped as follows: control; did not receive any type of treatment , control positive received single daily oral dose of 5 mg/kg ZnONPs in suspension, diabetic rats; received a single intra peritoneal dose of streptozotocin (50 mg/kg), diabetic + insulin; received a single daily subcutaneous dose of insulin (2U/kg) , diabetic + ZnONPs I, received single daily oral dose of 5mg/kg ZnONPs in suspension, diabetic + ZnONPs II, received single daily oral dose of 10mg/kg ZnONPs in suspension , diabetic+ ZnONPs + insulin I; received single daily oral dose of 5mg/kg ZnONPs in suspension and a single daily subcutaneous dose of insulin (2U/kg) and diabetic+ ZnONPs + insulin II; received single daily oral dose of 10mg/kg ZnONPs in suspension and a single daily subcutaneous dose of insulin (2U/kg) . The blood glucose , serum insulin, malondialdehyd (MDA) and serum nitric oxide (NO) levels were determined after 15 and 30 days of ZnONPs and/ or insulin treatment. The results indicated that the blood glucose, serum insulin, MDA and NO levels were increased while serum insulin levels were decreased in diabetic rats, while they are significantly modified in rats that administrated ZnONPs and/or insulin in a dose dependent. In conclusion, zinc oxide nanoparticles act as potent antidiabetic through decreasing of blood glucose and increasing of serum insulin as well inhibition of lipid and protein free radicals.