Osteoporosis is a metabolic bone disease affecting mostly elderly women. As metabolizing enzymes, the roles of few cytochromes have been studied in osteoporosis development. The aim of this study was to assess for the first time the association of CYP2E1 and CYP1A1 polymorphisms and osteoporosis in postmenopausal women. 112 postmenopausal women presenting osteoporosis and 93 age and sex matched healthy controls originating from north Iran were enrolled in this study. Rs2031920 and rs3813867 at CYP2E1 as well as rs4646421 and rs2198843 at CYP1A1 loci were studied in all subjects using polymerase chain reaction and restriction fragment length polymorphism analysis. Genotype analysis for rs2031920 showed that the CT genotype was present only in osteoporotic patients with a frequency of 4.17%. Similarly GC genotype at rs3813867 locus was present only in osteoporotic patients with a frequency of 3.13%. [G T] and [C C] haplotypes for rs3813867- rs2031920 were found with low frequencies only in osteoporotic patients. TT genotype at rs4646421 locus was higher in osteoporotic (8.05%) versus control subjects (3.22%), 14.28% of cases were homozygous for the C allele at rs2198843 locus which is higher than controls (11.84%). The [C G] haplotype for rs4646421- rs2198843 was predominant in cases (54.47%) and controls (58.6%). GT haplotype was rare in both groups. No significant differences in genotypes or haplotypes frequencies were observed among the osteoporotic and normal subjects. CYP1A1 and CYP2E1 loci are not associated to osteoporosis risk in the studied population.