Objective：This article aims to analyze the differences in efficacy and safety of recombinant human growth hormone (rhGH) treatment in children with idiopathic short stature (ISS) with different body mass indexes (BMI). Methods: ISS patients who received rhGH treatment at the First Affiliated Hospital of Hebei North University were selected as the research subjects. According to the growth standards for children under 7 years old and the gender age specific body mass index (BMI) overweight and obesity thresholds for Chinese school aged children and adolescents aged 6~18, ISS patients were divided into normal BMI group, overweight group and obese group. The height (Ht), body mass index (BMI), growth velocity (GV), height standard deviation score (HtSDS), insulin like growth factor-1 (IGF-1), insulin like growth factor binding-protein-3 (IGFBP-3), fasting blood glucose (FBG), thyroid function and liver function of three groups were measured before treatment, 3 months after treatment, and 6 months after treatment. Results: After rhGH treatment, the levels of Ht, GV, HtSDS, IGF-1, and IGFBP-3 in the three groups of ISS patients increased compared to before treatment (P<0.05). The amount of increase in Ht, GV, and HtSDS in children with normal BMI were significantly higher than those in the overweight and obese groups (P<0.05), while there was no significant difference between the overweight group and obese group (P>0.05). After 6 months of treatment, the BMI of children with normal BMI increased compared to before treatment (P<0.05), while the BMI of overweight group and obese group decreased compared to before (P<0.05). rhGH treatment has no significant effect on fasting blood glucose, thyroid function and liver function. Conclusion: rhGH can significantly increase the levels of Ht, HtSDS, GV, IGF-1, and IGFBP-3 in children with ISS. The therapeutic effect of ISS patients with normal BMI is significantly better than that of overweight group and obese group. There is no significant difference in the therapeutic effect between overweight and obese ISS patients, and rhGH treatment has great safety.