An ovoid reversible lesion in the central portion of the splenium of the corpus callosum without any accompanying lesions in MRI was uncommon in patients with encephalitis. We aim to report a virus-related encephalitis patient presenting with a reversible isolated ovoid lesion in splenium, mimicking acute infarction.A 32 years old previously healthy man suffered from intermittent fever up to 39°C accompanied with severe headache, drowsy consciousness, vomiting and diarrhea 2 days before admission. CSF study showed lymphocyte-predominant pleocytosis (lymphocyte/neutrophil 9/0), elevated level of protein (120mg/dL) but normal sugar level (42mg/dL). PCR for HSV-1/2, TB, and influenza antigen were negative. He was diagnosed as possibly virus-related encephalitis and receiving intravenous Acyclovir treatment. Brain MRI showed leptomeningeal enhancement. Notably, one 2.4cm-sized focal lesion with hyperintensity in diffusion weighted image (DWI) and hypointensity in apparent diffusion coefficient (ADC) was noted near the splenium of the corpus callosum, mimicking acute cerebral infarction. Intravenous Acyclovir was kept use and anti-tuberculosis agent (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) were added. His consciousness gradually recovered 2 weeks after treatment and there was no any neurological sequel left. Follow-up MRI 2 months later was normal without any residual lesions.Our case confirmed with previous findings that a reversible stroke-like splenial lesion could be seen in virus related encephalopathy and regarded as a good prognosis marker. Transient intramyelinic edema or inflammatory infiltrate is the possible mechanism and further studies enrolling more related cases will be needed to confirm our finding.