Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Fiber tracts passing through 54 anatomical sites in 12 adult mTLE patients and 12 age- and gender-matched controls were identified using DTI tractography. DTI nodal degree (ND) and laterality index were then calculated. ND laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p<;0.025). None of these anatomical sites showed statistically significant differences in ND laterality between right and left sides of the controls. Laterality models determined by logistic regression on the ND laterality data agreed with the side of epileptogenicity as it pertained to the gyrus rectus, insular cortex, precuneus and superior temporal gyrus for 89%, 72%, 83% and 92% of the patients, respectively. Combining the laterality measures in these four anatomical sites improved the results further with correct lateralization of 100% for all patients. The proposed methodology for using DTI connectivity to investigate diffusion abnormalities related to focal epileptogenicity and propagation can provide a further means of noninvasive lateralization.