Objective: The aims of this study were as follows: 1) to evaluate the association of serum sclerostin with bone mineral density (BMD) and markers of bone metabolism in postmenopausal Chinese women and 2) to observe the relationships of single-nucleotide polymorphisms (SNPs) within the sclerostin (SOST) gene with serum sclerostin, BMD, and markers of bone metabolism. Design: A cross-sectional study was conducted with 703 postmenopausal Chinese women. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. Serum sclerostin and markers of bone metabolism were measured, including serum intact PTH, 25-hydroxyvitamin D [25(OH) D], procollagen type 1 N-terminal propeptide, and beta-CrossLaps of type I collagen containing crosslinked C-telopeptide (beta-CTX). The BMD of the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry. Results: Serum sclerostin was positively correlated with BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH) D (all P < .01) but negatively correlated with beta-CTX (P < .01). The significant relationships between serum sclerostin and BMD and with serum beta-CTX persisted, even after adjustments for age, body mass index, and serum 25(OH) D (all P < .01). However, there was no correlation between serum sclerostin and age or serum procollagen type 1 N-terminal propeptide. We failed to identify a significant association between the SNP, haplotypes of SOST and BMD, or serum sclerostin. Conclusion: Our results suggested that serum sclerostin was positively correlated with the BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH) D but was negatively correlated with serum beta-CTX. Genetic polymorphisms of SOST may not be a major contributor to variations in the serum sclerostin or BMD in postmenopausal Chinese women.