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Objective: Human multiple sclerosis (MS) is a complex disease and demyelinated lesions in central nervous system (CNS) are the pathologic hallmark of MS. Remyelination occurs in many MS lesions but becomes increasingly incomplete/inadequate. Protein tyrosine phosphatase,receptor-type z polypeptid1 (PTPRZ1) has been implicated in adult cell renewal, repair of the nervous system, oligodendrocyte development and so in Remyelination. We investigated possible association of multiple sclerosis with polymorphism of two SNPs (rs13241278 and rs2693657) located in PTPRZ1 gene. Materials and Methods: Peripheral blood was collected from 140 subjects with MS and 165 healthy controls and DNA was extracted. For genotyping of rs13241278 and rs26936575, PCR-RFLP and mismatch PCR-RFLP techniques were used, respectively. Association of SNPrs13241278 and SNPrs26936575 with multiple sclerosis was examined by using the Chi-square test and the frequency differences of alleles and genotypes between two groups were compared. A conventional p-value of ≤ 0.05 was considered significant. Results: Statistical analyses on two studied polymorphisms showed that both case and control group were in Hardy-Weinberg equilibrium. By using χ2 test, the difference between frequency of SNPrs13241278 Risk allele vs. other allele in control and case groups was p=0.377 and for SNPrs26936575 was p=0.669. The difference between frequency of Homozygosity vs. other genotypes in control and case groups for SNPrs13241278 was p=0.377 and for SNPrs26936575 was p=0.64. Conclusion: According to the χ2 test results, the differences were not significant for studied SNPs. As a conclusion, we did not find association between SNPrs1 3241278 and SNPrs26936575 of PTPRZ1 and multiple sclerosis in Iranian population. [ABSTRACT FROM AUTHOR]