Abstract： Aim To investigate the serum levels of insulin-like growth factor binding protein-3(IGFBP-3),25 hydroxyvita-min D[25(OH)D],food intake inhibitory factor-1(Nesfatin-1),and osteocalcin in children with idiopathic short stature(ISS)and their clinical significance.Methods 286 children with short stature were selected as the observation group,including 152 cases in the ISS group and 134 cases in the growth hormone deficiency(GHD)group.Meanwhile,100 healthy children were selected as the control group.The differences in serum IGFBP-3,25(OH)D,Nesfatin-1,and osteocalcin levels among different groups were compared,and their relationship with physical development was analyzed.Results The height,bone age index,serum IGFBP-3,25(OH)D,and osteocalcin levels of children in the observation group were lower than those in the control group,while Nesfatin-1 was higher than that in the control group(P＜0.05).The height,bone age index,serum IGFBP-3,25(OH)D,and osteocalcin of chil-dren in the ISS group were higher than those in the GHD group,while Nesfatin-1 was lower than that in the GHD group(P＜0.05).Serum IGFBP-3,25(OH)D,and osteocalcin levels were higher in children with a height of ≥125 cm than those in children with a height of＜125 cm,and higher in children with a bone age index of≥0.90 than those in children with a height of＜0.90.However,the trend of Nesfatin-1 is opposite(P＜0.05).The serum levels of IGFBP-3,25(OH)D,and osteocalcin in children with ISS were positively correlated with their height and bone age index(P＜0.05),while Nesfatin-1 was negatively correlated with their height and bone age index(P＜0.05).Conclusion Compared with healthy children,the serum levels of IGFBP-3,25(OH)D,and osteocalcin in children with ISS are lower,while the levels of Nesfatin-1 are higher,which may be related to the physical development of children.