Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.