Background: One of Multiple sclerosis (MS) presumed pathological mechanisms is failure of apoptosis of autoreactive T lymphocytes. Objectives: To determine the relationship between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA gene expression ratio and serum TRAIL levels with MS susceptibility and brain atrophy. Materials and methods: This study was conducted on 53 relapsing remitting MS patients and 25 matched healthy volunteers. The expression of TRAIL on peripheral blood lymphocytes was analyzed by RT-PCR, serum levels of soluble TRAIL (sTRAIL) was determined by ELISA and MRI brain for measurement of black holes and the bicaudate ratio (BCR) as a measure of brain atrophy were done for all patients. Results: The sTRAIL level was lower in MS patients compared to the control but no difference was found in the TRAIL mRNA gene expression ratio. A positive correlation was found between EDSS and age of patients while a negative correlation was found between progression index and both disease duration and BCR. Conclusion: Apoptosis of T lymphocytes is deficient in MS patients which can be implicated in the treatment. No difference between TRAIL mRNA gene expression ratio between MS patients and controls.