The peroxisome proliferator-activated receptor γ (PPARγ) protein as well as its transcript was detected in primary osteoblasts derived from rat calvariae. To analyze the possible involvement of PPARγ in the human bone metabolism, association between bone mineral density (BMD) and a polymorphism of PPARγ gene was investigated in Japanese postmenopausal women. We examined a polymorphism corresponding to a silent C → T transition located in exon 6 of the PPARγ gene, that was previously reported to be associated with plasma leptin levels in the obese. The frequencies of the C and T alleles in the population studied here were 0.851 and 0.149, respectively. When we separated the subjects into two groups, one bearing at least one T allele (CT + TT) and the other which did not (CC), the former subjects had lower BMD (Z score of total body; 0.056 ± 1.00. L2-4; −0.25 ± 1.26, mean ± standard deviation). These data suggest that there is an association between the restriction fragment length polymorphism (RFLP) of PPARγ gene and BMD and the possible involvement of this single nucleotide polymorphism (SNP) in the cause of postmenopausal osteoporosis in Japanese women.