Diffusion fMRI (DfMRI) is a powerful functional imaging method to investigate neural activity and network without BOLD confounding hemodynamic effects. In this study, we applied DfMRI to evaluate brain activity and network of neuropsychiatric disease model, obsessive–compulsive disorder (OCD). Our DfMRI study revealed that the cortex was excited and the hippocampus was inhibited. Functional connectivity analysis of DfMRI detected alterations of cortico-striatal-thalamic networks, in line with the previous study with OCD patients. Additionally, we found that interesting network alterations of the hippocampal networks in this OCD model mice.