Abstract: Multiple Sclerosis (MS) is an autoimmune nervous system disorder characterized by leukocytes recruitment into nervous system and demyelination. Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein, which is expressed by activated endothelium in a variety of pathologic conditions including MS. The aim of this study (case-control) was to evaluate the probable association of VCAM-1 T-1594C and A-540G single nucleotide polymorphisms (SNPs) with circulating levels of sVCAM-1 and susceptibility to MS. Analysis of VCAM-1 polymorphisms was performed by PCR with Sequence-Specific Primers (SSP) and concentration of sVCAM-1 in serum was performed by ELISA techniques. No significant differences were detected for allele frequencies of VCAM-1 polymorphisms in MS patients than in the controls respectively (p>0.05). Moreover, baseline serum sVCAM-1 concentrations significantly increased among patient in contrast to controls (p<0.001). This study shows that these SNPs in VCAM-1 my not a putative risk predisposing alleles for MS and its clinical covariates in southeast Iran population. The folding rate of the VCAM-1 protein increases for MS patients implicating a potential effect and function of VCAM-1 in immunopathogenesis of MS. Results invites further investigation relevant to understanding the mechanisms underlying the VCAM-1 overexpression in MS patients.