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The authors report serial brain MR findings from a 2-year-old girl with rotavirus encephalopathy. The lesion in the splenium of the corpus callosum showed restricted proton diffusion, suggesting local cytotoxic edema. Diffusion-weighted images demonstrated the lesion more conspicuously than other techniques, such as fluid-attenuated inversion-recovery and T1- and T2-weighted images. The findings were reversible on follow-up MRI obtained 4 days later. Diffusion-weighted MRI is a potentially useful method for detecting early changes of rotavirus encephalopathy, although the mechanism of the restricted diffusion is not clearly identified.