Purpose: This study aimed to investigate whether Fractional Anisotropy (FA) is reliable in detecting hippocampal sclerosis on intractable Mesial Temporal Lobe Epilepsy (MTLE) with normal MRI as measured from the degree of of neuronal loss, gliosis and axonal sprouting. Method: Twenty-three MTLE patients underwent surgery and 10 healthy volunteers were involved in this study. The MTLE diagnosis was based on semiology and ictal EEG, while hippocampal sclerosis was diagnosed using standardized MRI, followed by DTI FA. Histopathological analysis of hippocampus was performed with NeuN, GFAP, and NPY staining to detect the neuronal loss, gliosis, and axonal sprouting. Correlation and Diagnostic test was done to asses of diagnostic value FA. Result: Ten MTLE patients showed normal MR, 4 with hippocampal sclerosis and 6 were with FCD. The value of FA was significantly lower compared with healthy subject. The cut-off point of FA in detecting hippocampal sclerosis was 0.17 (AUC=0.89). The sensitiviy, specificity, positive predictive value, and negative predictive value of FA were 81.8%, 72.3%, 64.3%, and 89.56% respectively. There was significantly correlation between FA with the degrees of neuronal loss and gliosis. The concurrence between FA with EEG 7 out of 10 patients. Conclusion: Fractional Anisotropy has a good diagnostic value in detecting hippocampal sclerosis on normal MRI patients. In addition, this technique also shows a moderate association with degrees of neuronal loss and gliosis.