Abstract Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are autoimmune demyelinating diseases of the CNS. Interleukin-7 (IL-7) and interleukin-7 receptor alpha (IL-7Ra) were suggested to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. Aim of Study: To investigate the association of IL-7Ra  (rs6897932) genotypes and serum level of IL7 with MS and NMO in a group of Egyptian patients. Patients and Methods: A cross-sectional case control study including 90 subjects (40 MS, 20 NMO patients and 30 healthy controls). IL-7Ra  (rs6897932) genotypes were studied by amplification refractory mutation system-polymerase chain reaction. Serum level of IL7 was measured by sandwich enzyme-linked immunosorbent assay. Results: This results suggested that CT genotype, combined CT and TT genotypes and T allele increases risk of MS in the sample of Egyptian population studied (OR 5.040, 95% CI 1.293-19.646; OR 5.400, 95% CI 1.395-20.907 and OR 4.75 95% CI 1.316-17.148, respectively). CT genotype, combined CT and TT genotypes and the T allele were found to be significantly higher in MS cases versus controls (p 0.02, 0.015 and 0.017, respectively). As for NMO, combined CT and TT genotypes and T allele increases risk of NMO (OR 4.846, 95% CI1.075-21.842 and OR 4.75, 95% CI 1.176-19.18 respectively). Combined CT and TT genotypes and T allele were significantly higher in NMO versus controls (p 0.04 and p 0.029, respectively). IL7 was significantly lower in the MS patients during the attacks than in MS patients in between attacks (p 0.030). Conclusion: T allele of IL-7Ra  (rs6897932) could be considered as susceptibility marker of MS and NMO in Egyptian patients. IL7 serum level might be involved in the pathogenesis of MS and NMO but assessment of its level in treatment of naïve patients is essential to prove it.