Objective: The study objective was to investigate the protective effects of dexrazoxane (DRZ) on the cardiac autonomic nervous system (ANS) activity in anthracycline-treated breast cancer patients with diabetes. Methods: A total of 110 early stage breast cancer patients with type 2 diabetes were divided randomly into 2 even groups: chemotherapy alone (Chemo) and chemotherapy+DRZ (Chemo + DRZ). All patients underwent adjuvant chemotherapy (80 mg/m(2) epirubicin and 500 mg/m(2) cyclophosphamide) for a total of 6 cycles with 21 days/cycle. The Chemo + DRZ group patients were treated intravenously with 800 mg/m(2) DRZ 30 minutes prior to the administration of epirubicin, while the Chemo group patients were given saline. The cardiac ANS function was evaluated for each patient before and after 6 cycles of chemotherapy by resting heart rate (RHR) and heart rate variability (HRV), which was evaluated by both time and frequency domains. Results: Before and after chemotherapy, patients in both groups showed significant decreases in HRV indices and increases in RHR and the low-frequency/high-frequency ratio. There were no significant differences between Chemo and Chemo + DRZ groups in terms of RHR and HRV indices before chemotherapy; however, after chemotherapy, patients in the Chemo group had a higher average RHR and lower HRV indices compared with patients in the Chemo+DRZ group. Conclusion: DRZ protects the cardiac ANS in epirubicin-treated early stage breast cancer patients with diabetes.