Encephalopathy associated with human herpes virus 6 infection (HHV-6 encephalopathy) is not rare. The pathophysiology of HHV-6 encephalopathy has not been clearly established and diagnosis in the early stages is difficult. To elucidate the diagnostic value of MRI in the early stages of HHV-6 encephalopathy, we performed MRI including diffusion weighted imaging (DWI) on 6 patients. No abnormalities were found in the T1, T2 weighted images and fluid attenuated inversion recovery (FLAIR) images of any of the patients. DWI revealed an increase of signal in the subcortical white matter of the frontal lobes during the acute phase in all 6 patients. Follow-up MRI in two patients showed lesions expanded to the cortical regions, and disappearance of high signal-lesions followed by atrophy of the corresponding areas in 2 patients. To our knowledge, these findings have not previously been reported in acute encephalopathy and encephalitis and may be characteristic of HHV-6 encephalopathy. DWI may be a useful diagnostic procedure in the early stages of HHV-6 encephalopathy.