Objective: This study aimed to explore the diagnostic points and treatment modes of the clinical characteristics of Japanese encephalitis (JE) in the middle-aged and elderly population. Methods: Six patients aged 47–72 who were diagnosed with JE at the Beijing Chaoyang Hospital Affiliated with the Capital Medical University between August 2018 and September 2019 were enrolled in the study. Their clinical manifestations, biochemical indicators, imaging data, diagnostic methods, and the evolution and outcomes of the treatments they underwent were retrospectively analyzed. Results: (1) All six patients had severe clinical symptoms and poor prognoses that were more likely to be associated with other systemic diseases. (2) Lesions were most commonly distributed in the thalamus, basal ganglia, and midbrain. The appearance of hyperintensity in the corpus callosum, hippocampus, and subcortical white matter was more specific. The hyperperfusion metabolism in the lesion area in head computed tomography perfusion imaging indicated the state of inflammatory activity in the lesion. In cranial magnetic resonance imaging (MRI), T2 and fluid-attenuated inversion recovery (FLAIR) were more sensitive. (3) After a patient has been systematically treated in the intensive care unit (ICU), the patient gradually recovered and the level of consciousness improved (p 0.05). Conclusions: In brain MRI—especially T2 and FLAIR—intracranial infection is often accompanied by abnormal signals in the thalamus, midbrain, hippocampus, and white matter hyperintensity (WMH), which is highly suggestive of JE. The positive detection of anti-JE virus immunoglobulin M antibodies in a patient’s serum and/or cerebrospinal fluid can confirm the diagnosis of JE, and comprehensive ICU treatment (hormones combined with anti-inflammatory, antiviral, and mild hypothermic cerebral protection therapies) can improve the survival rate.