Diabetic cardiomyopathy (DCM) can lead to left ventricular hypertrophy, diastolic dysfunction, and systolic dysfunction, or all of these. Gold nanoparticles (AuNPs) have shown anti-hyperglycemic effects in animal models of streptozotocin (STZ)-induced diabetes. This study was designed to address the effects of AuNPs on the animal model of DCM. twenty-two male adult rats were randomly categorized into 3 groups (n=6-8 / group): control (non-diabetic, ND), diabetic (D), and intraperitoneally treated diabetic rats with 50 nm AuNPs (D+AuNPs; 2,5 mg/kg/day). One single dose injection of 55 mg/kg STZ was used to induce diabetes in the animals. Blood and the left ventricle were collected after seven weeks for assessment. The myocardial mRNA and protein levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were evaluated using real-time PCR and immunohistochemistry. The myocardial mRNA level of vascular endothelial growth factor-A (VEGF-A) was measured using real-time PCR. Besides, the myocardial collagen deposition was measured by masson trichrome stain and immunohistochemistry. Rats with DCM showed hyperglycemia, increased myocardial mRNA and protein tissue content of TGF-β1, myocardial mRNA of VEGF-A (P < 0.05), and tended to increase myocardial mRNA and protein tissue content of TNF-α (P < 0.1). An increase in myocardial collagen deposition accompanied these changes. Treatment with AuNPs reduced the above pathological conditions. These results suggest that AuNPs may have therapeutic potential in the treatment of early DCM. Further studies are needed to explore the possible mechanisms by which AuNPs may prevent the development of DCM.