Background With the significant improvement in the survival of patients with nasopharyngeal carcinoma (NPC)undergoing radiotherapy and the growing availability of the sophisticated imaging modalities, the number of radiation encephalopathy (RE) cases relating to NPC radiotherapy is increasing. In this study, we investigated the metabolic and density changes of the compromised brain tissues during delayed RE using a positron-emission tomography-computed tomography (PET/CT) to provide clinical evidences for the diagnosis of delayed RE following radiotherapy for NPC.Methods The PET/CT manifestations and the clinical data of 53 pathologically confirmed NPC patients with delayed RE following radical radiotherapy and 15 healthy volunteers were investigated. The standardized uptake values (SUV) of the bilateral temporal lobes, the occipital lobe and the brain stem were measured respectively; and then the metabolic reduction rate of 88 temporal lobes and 13 brain stems were calculated for a statistical comparison between the two groups.Results The earliest case of delayed RE in the investigated patients occurred 1.5 years after radiotherapy. Delayed RE frequently involved the inferior temporal lobe. For patients with delayed RE confirmed by clinical symptoms and imaging findings, PET maintained a 100% coincidence rate with CT; however, in the 25 temporal lobes of the 35 delayed RE patients, PET revealed obvious hypometabolic changes whereas CT displayed normal density. The incidence of brain stem metabolic reductions was 24.5% (13/53) in the investigated patients, including 4 patients with hypometabolic changes shown by PET and negative finding shown by CT. The incidence of granuloma adjacent to the hypometabolic region in the temporal lobe was 12.5% (11/88).Conclusion Delayed RE patients exhibit significant hypometabolic changes in the inferior temporal lobe, captured by PET much earlier than by CT. PET/CT offers a valuable means for the diagnosis of delayed RE in subacute stages and granuloma formation.