Background Serum leptin concentration is associated with age, fat and bone mineral density (BMD), and there are ethnic differences in physique and BMD values. The relationship between serum leptin concentration and BMD in Chinese women is presently unknown. We examined the relationship of serum leptin concentration with age, body weight, BMI and BMD in mainland Chinese women. Methods Serum leptin concentration in a population of 676 Chinese females, aged 20–80 years (45.4±14.8 years, mean±S.D.), was measured using an enzyme-linked immunosorbent assay (ELISA). BMD values were measured by dual-energy X-ray absorptiometry (DXA) at a number of sites: the posteroanterior lumbar spine (PA, L1–L4), lateral lumbar spine (Lat, L2–L4), hip (including the femoral neck (FN) and total hip (T-hip)), and forearm (one-third region (RU1/3) and total region (RUT)). The relationship between changes in serum leptin concentration with age, body weight, height, body mass index (BMI) and BMD values at six sites were analyzed using 10 different regression models, and the models giving the best fit were selected. Results The cubic regression model best described the changes in serum leptin concentration with age ( R 2=0.048, p<0.001) and body weight ( R 2=0.352, p<0.001), while the quadratic regression model was best for serum leptin concentration changes with BMI ( R 2=0.410, p<0.001); serum leptin concentration was not correlated with height. Serum leptin concentration was significantly higher in postmenopausal than premenopausal women ( p<0.001). Serum leptin concentration was correlated with Lat BMD ( R 2=0.012, p<0.018), FN BMD ( R 2=0.006, p<0.041) and T-hip BMD ( R 2=0.013, p<0.004) in the whole population. In premenopausal women, leptin was positively associated with BMD except for Lat ( R 2=0.029–0.055, p<0.008); in postmenopausal women, leptin was also positively associated with AP, FN, T-hip BMD ( R 2=0.026–0.042, p<0.007). However, after adjusting for BMI not for body weight, there was no association between serum leptin concentration and age. Meanwhile, after adjustment for age, body weight and BMI, there was no association between serum leptin concentration and BMD values in premenopausal and postmenopausal women. Conclusions Age-related changes in serum leptin concentration is dependent on BMI, but not a direct determinant of BMD in Chinese females.