Patients with type 2 diabetes mellitus (T2DM) have usually been found cognitive impairment associated with brain white matter (WM) abnormalities. However, findings have varied across studies, and any potential relationship with Alzheimer's disease (AD) remains unclear. The aim of this study was to assess the whole-brain WM integrity of T2DM patients and to compare our findings with those of published AD cases. In this study, we used diffusion tensor imaging (DTI) combined with tract-based spatial statistics (TBSS) to investigate whole-brain WM abnormalities in 48 T2DM patients and 48 healthy controls. The effects of age and gender were also evaluated. In our study, significantly decreasing FA and increasing MD and DA values (P<0.05) were found in some WM regions closely related to the default mode network (DMN), including cingulum, the right frontal lobe involving the right uncinate fasciculus (UF), bilateral parietal lobes involving the superior longitudinal fasciculus (SLF) and the inferior longitudinal fasciculus (ILF), and the right middle temporal gyrus (MTG) involving the UF and the ILF. We also found abnormalities in the thalamus involving the fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR). The damaged regions above are similar to those found in patients with AD, as reported in previous studies. The present study not only provides useful information about the WM regions and tracts affected by T2DM but also offers insight into the underlying neuropathological process in T2DM patients and the relationship between T2DM and AD.