Reversible corpus callosum splenial (CCS) lesions have been described in patients with varied etiologies. The most common causes of previously reported reversible focal lesions of the CCS are viral encephalitis, antiepileptic drug toxicity/withdrawal, and metabolic disorders. Intravenous immunoglobulin (IVIG) therapy is used for different immune-mediated diseases. It is generally safe, and serious adverse reactions are uncommon. We presented a rare case of disturbed consciousness with reversible CCS lesions after IVIG therapy for Guillain-Barre syndrome in an adult woman. In this case, we believe that IVIG therapy caused reversible CCS lesions with encephalopathy and probably result of cytotoxic edema and/or cerebral arterial vasospasm.