The objective of this study was to evaluate whether water apparent diffusion coefficient (ADC) measurements provide more specific information than T2-weighted MRI about the evolution of brain parenchyma lesions secondary to prolonged complex partial seizures. We measured the ADC in the brain of rats exhibiting prolonged complex partial seizures induced by intraperitoneal injection of kainic acid (KA). The animals were imaged with diffusion and T2-weighted MRI at 2 T from 3 h up to 9 days after KA injection. In the piriform cortex and amygdala, the T2-weighted MRI signal intensity appeared to be uniformly increased from 24 to 72 h after KA injection, and returned to normal by 9 days. In the same regions between 24 and 72 h, the ADC first decreased and then increased. The ADC changes were consistent with the known histopathologic alterations. In this complex partial seizure model, the ADC measurement provides more specific information than T2-weighted MRI about the histopathologic evolution of the lesions. This supports the proposal that diffusion MRI may be valuable for the evaluation of the neuropathologic sequelae in patients with multiple or prolonged seizures.