The objective of the study is to investigate the association of rs2229579 polymorphism of cannabinoid receptor 2 gene (CNR2) with bone mineral density (BMD) in Chinese Han postmenopausal women. 490 Chinese Han postmenopausal women were randomly recruited and their BMD were measured by dual-energy X-ray absorptiometry (DEXA) at total body, lumbar spine (L2-L4), femoral neck and trochanter. Genotypes for the CNR2 rs2229579 were determined by polymerase-chain-reaction with the confronting-two-primer (PCR-CTPP). The genotypes distribution of CNR2 rs2229579 was met with Hardy-Weinberg equilibrium (P>0.05). The allelic frequencies for the 490 Chinese Han postmenopausal women were 82.8% for C and 17.2% for T in CNR2 rs2229579 polymorphisms. The prevalence of each genotype in the study population was 67.8% CC, 30.0% CT, and 2.2% TT. BMD for both of femoral neck and total body in women with TT genotype was significantly higher than those with CC, CT and combined group of CC and CT genotypes, respectively (all the P values <0.05). T-score at femoral neck in women with TT genotype was higher than those with combined group of CC and CT genotypes (P<0.05). T-score at total body in women with CC genotype was lower than those with combined group of CT and TT genotypes (P<0.05). There were no genotypes or alleles distribution differences in CC, CT and TT genotypes between osteoporosis and control group (X-2 = 0.750, P > 0.05; X-2 = 1.804, P > 0.05). Our results suggest that there is a significant association between CNR2 rs2229579 genotype polymorphisms and BMD, as well as t-score in Chinese Han postmenopausal women. This suggests that CNR2 rs2229579 may play a role in osteoporosis pathogenesis.