Background Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. In recent years, cerebellum abnormalities in mental disorder are receiving increasing attention [1-4]. It is a critical structure (including superior cerebellar peduncles, middle cerebellar peduncles and dentate nuclei) in the prefrontal-thalamic-cerebellar circuit which is related to both cognitive and affective functions [5, 6]. This circuit has been found to be abnormal in patients with schizophrenia in structural [7] and functional [5, 8] neuroimaging studies. However, little is known about the similarities and differences in cerebellum between BD and UD. Methods Patients with BD (n = 35) and UD (n = 30) during a depressive episode as well as 40 healthy controls underwent diffusional kurtosis imaging (DKI) and three dimensional arterial spin labeling (3D ASL). The DKI parameters including mean kurtosis (MK), axial kurtosis(Ka), radial kurtosis (Kr),fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) and 3D ASL parameters (i.e. cerebral blood flow) was measured by using regions-of-interest (ROIs) analysis in the superior cerebellar peduncles(SCP), middle cerebellar peduncles (MCP) and dentate nuclei (DN) of cerebellum. ROIs were determined by two independent neuroradiologists who were blinded to the patient or control status and manually placed in the bilateral SCP, MCP, and DN of the cerebellum on the maximum level of the three separate ROIs (fig1a-f). All ROIs of DKI parameters were then transferred to the maps of MK, Ka, Kr, FA, MD, Da, and Dr while the ROIs of 3D ASL were transferred to the maps of CBF for measurement. Results Patients with UD exhibited significant differences from controls for DKI measures in bilateral SCP and MCP and cerebral blood flow (CBF) in bilateral SCP and left DN. Patients with BD exhibited significant differences from controls for DKI measures in the right MCP and left DN and CBF in the left DN. Patients with UD showed significantly lower MD values compared with patients with BD in the right SCP (fig2a-f, fig3a-b). Correlation analysis showed there were negative correlations between illness duration and MD and Dr values in the right SCP in UD, and negative correlations between illness duration and CBF in bilateral SCP in BD (fig4a-d). Discussion and conclusions The current study, to our knowledge, is the first to reveal the potentially important role for SCP, MCP and DN of cerebellum in BD and UD. Our results suggest that these two disorders may have overlaps in microstructural and functional abnormality in MCP and DN during the depressive period. Microstructural abnormality in SCP may be a key neurobiological feature of UD. Returning to the hypothesis posed at the beginning of this study, it is now possible to state that microstructural abnormalities and CBF changes of the cerebellum in prefrontal-thalamic-cerebellar circuitry play a key role in neurobiological process in patient with BD and UD.