Abstract: Objective To investigate the changes of heart rate variability (HRV) in patients with type 2 diabetes mellitus and the effects of epalrestat on HRV. Methods Twenty-four hour Holter monitoring was conducted in 46 type 2 diabetic patients and compared with that in 28 healthy controls. All the 46 type 2 diabetic cases were randomly divided into conventional treatment group and epalrestat group. The epalrestat group was given epalrestat in addition to conventional treatment. HRV was observed after 6 months. Indices of HRV, including time domain indices and frequency domain indices, were observed. The time domain indices were as follows:24 h standard deviation of all normal to normal RR intervals (SDNN), standard deviation of 5 min mean RR intervals (SDANN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD), percentage of successive normal RR intervals exceeding50 ms (p NN50). The frequency domain indices were as follow:LF, HF and LF/HF. Results There were significant difference in the time domain indices and frequency domain indices of HRV between healthy controls and type 2 diabetic patients (P<0.01). After 6 months of treatment, SDNN, SDANN, rMSSD, PNN50, LF, HF and LF/H were not improve in the control group (P>O. 05), however, all the time domain indices and frequency domain indices in the epalrestat group were all significantly improved, the differences were statistically significant (P<0.05). Conclusion The HRV decreases and the function of autonomic nervous system was impaired in patients with diabetic mellitus. Epalrestat may improve the function of autonomic nervous system in patients with diabetic patients.