Imaging changes in patients with focal epilepsy are not only seen in areas where seizures arise but often also in remote locations. The mechanism for such changes is unknown. We aimed to investigate whether patients with temporal lobe epilepsy (TLE) have microstructural changes involving the posterior portion of the corpus callosum (CC), where it links the temporal lobes, using presurgical diffusion tensor imaging (DTI) sequences. Ten patients with medically intractable TLE (two mesial TLE, eight neocortical TLE) who had seizure-free surgical outcomes were compared with 10 healthy controls. The regions of interest were outlined at each Witelson region (WR). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and three principal diffusivity values (lambda1, lambda2, lambda3) were determined in each WR. We performed tractography originating at each WR. In the TLE patients, the FA values were lower at the splenium of the corpus callosum (WR 7) compared to controls (p<0.05). Analysis of Eigen values in that location revealed that lambda1 values were decreased while lambda2 and lambda3 values were increased (p<0.05). Tractography revealed the connection between both temporal lobes via WR 7. In conclusion, decreased FA values with decreased lambda1 and increased lambda2 and lambda3 at the splenium of CC suggest that the pathologic changes, Wallerian degeneration, extend to the corpus callosum in TLE patients. Seizure-induced damage may cause secondary white matter degeneration along the tapetum and through the splenium of the corpus callosum, a potential pathway of spread in temporal lobe seizures.