Objective To investigate the clinical and radiological characteristics of reversible posterior leukoencephalopathy syndrome (RPLS) and to provide a reference for the differentiation between RPLS and toxic encephalopathy.Methods A retrospective analysis was performed on the clinical characteristics, imaging data, and treatment of 6 patients with RPLS.Results The 6 patients had histories of drinking, taking heroin, gas poisoning, long-term exposure to paint coatings, inhaling carbon monoxide, and exposure to organic solvent. The clinical manifestations mainly included headache, nausea, vomiting, seizures, and hypertension. Head MRI showed lesions in both temporal lobes, parietal lobe, frontal lobe, periventricular white matter, cerebellum, and brainstem, and the signals were long T1 and long T2 with no enhancement. After symptomatic treatment and treatment for removing the cause of disease, the 6 cases showed significant improvements in both clinical manifestations and imaging findings.Conclusions Patients with RPLS may manifest clinical and imaging features similar to those of toxic encephalopathy, especially when patients have histories of inhaling poisonous substances. The disease should be excluded as early as possible based on its clinical and radiological characteristics as well as the treatment outcome.