Diabetic cardiomyopathy (DMCM) is characterized by an early left ventricular (LV) diastolic dysfunction and subsequent progression to systolic dysfunction. In this study, we hypothesized the downregulation of cardioprotective factors is involved in the pathogenesis of DMCM. We aimed to elucidate the mechanisms underlying the DMCM development. In the streptozotocin (STZ)-induced type 1 diabetic model mice 4 weeks after STZ injection (STZ-4W), diastolic function was impaired without systolic dysfunction. Counter to expectations, the serum levels of neuregulin-1 (NRG1) were significantly up-regulated in the STZ-4W group compared to the control group. NRG1 expression was increased in the ventricle, kidney, and liver in the STZ-4W group. In the ventricles, NRG1 was localized in the vascular endothelial cells, endocardium, and epicardium. To clarify the physiological role of NRG1, trastuzumab (TRZ), an antibody against NRG1 receptor ErbB2 (HER2), was administered to mice. The systolic function, T-tubule structure, and the accumulation of Ca_V1.2 at the junctional structure were significantly impaired in the TRZ-injected STZ-4W mice compared to STZ-4W mice. These results suggest that the compensatory up-regulation of NRG1-ErbB signaling contributes to maintaining the LV systolic function in the early stage of DMCM.