Diabetic cardiomyopathy was the most dangerous diabetic complication facing diabetics, with its exact mechanisms remaining obscure. Our study was conducted to investigate the expression of thrombospondin-1 (TSP-1) and neuropeptide Y (NPY) in myocardium of streptozotocin (STZ)-induced diabetic rats. We employed streptozotocin (STZ)-induced diabetic rats to study the alteration of the TSP-1 and NPY expression in the left ventricle myocardium in diabetic and normal group by immunohistochemistry and immunofluorescence. The data of weight, blood sugar and urine sugar indicated no significant difference between the two groups before the animal model was induced. Four weeks after the induction of diabetes the weight of the diabeteic animals was 189.1+/-18.4 g, plasma glucose was 23.7+/-3.25 mmol/L and urine glucose was (++) to (+++); whereas the weight of the control animals was 260.5+/-32.1 g, plasma glucose was 4.9+/-0.5 mmol/L and urine glucose undetectable (-). The differences between the control and the diabetes group were distinct. A significant increase of the TSP-1 and NPY expression was also observed in the diabetic rat's heart. The number of the NPY positive myocardium and the light density of the positive myocardium in the left ventricle of the diabetic model were 17.3+/-2.1 and 102.5+/-9.3/mm(2), respectively, which were considered as increased when compared with the control that were 10.1+/-2.6 and 61.2+/-6.7, respectively. Our results support the view that high glucose conditions can induce an increased synthesis of TSP-1 through the PKC-TGF-beta-TSP-1 pathway, which in turn facilitate TGF-beta activation. Additionally, the activation of PKC may further lead to the over-expression of NPY. This may be involved in diabetic cardiomyopathy.