To investigate the etiology, clinical manifestations, and imaging features of reversible splenial lesion syndrome (RESLES). Methods: The clinical data of 3 cases of RESLES diagnosed in our hospital and 128 cases reported in domestic literature were retrospectively analyzed. Results: Of the 131 patients, 88 were adults, including 54 males and 34 females, and the average age was 29.27 years. The remaining 43 patients were children, including 24 males and 19 females, with an average age of 5.46 years. The cause of RESLES in both adults and children was mainly infection, accounting for 64.78% and 83.72%, respectively, of which viral infection is the main cause. Primary clinical manifestations in adults were fever (65.91%), headache (47.73%), disturbance of consciousness (27.27%), convulsions (20.45%), visual impairment (12.5%), abnormal mental behavior (12.5%), and cognitive dysfunction (10.23%). In children, major clinical manifestations included fever (53.49%), convulsions (58.14%), disturbance of consciousness (53.49%), and headache (27.91%). Cranial MRI showed reversible lesions in the splenium of corpus callosum (patchy iso-or hypo-intensity on T1WI and ADC and hyper-intensity on T2WI，FLAIR, and DWI). The average time for disappearance of lesions for adults was 19.5 days and for children 14.9 days. There were 22.73% of adults and 9.30% of children with lesions outside the corpus callosum. Conclusion: The etiology of RESLES is complicated. It can be divided into infected and non-infected categories according to whether it is infectious. The clinical manifestations are non-specific, and imaging features include characteristic reversible changes. The general prognosis is good.