Objective To study the relationship between the expression of suppressor of cytokine signaling 3 (SOCS3) and the response to glucocorticoid(GC) treatment in children with primary nephrotic syndrome(PNS). Methods Peripheral venous blood samples were collected from 30 children with steroid-sensitive nephrotic syndrome (SSNS), 16 children with steroid-resistant nephrotic syndrome(SRNS) before and after GC treatment, and 16 healthy children. The expression of SOCS3 mRNA in peripheral blood monocytes (PBMC) and the expression of SOCS3 protein in plasma were detected. At the same time, the 24-hour urine protein, serum creatinine, blood urea nitrogen and glomerular filtration rate were measured before and after GC treatment in PNS children, and their correlation with SOCS3 expression was analyzed. Results Before GC treatment, the SSNS and SRNS groups had significantly higher mRNA and protein expression levels of SOCS3 than those of childen in the control group (P<0.05). After 6 weeks of GC treatment, the mRNA and protein levels of SOCS3 in SSNS group were lower than those before treatment (P<0.05), and the mRNA expression of SOCS3 in SRNS group showed no significant change compared with pre-treatment period (P>0.05), and the protein level of SOCS3 was increased compared to pre-treatment (P<0.05).Before and after GC treatment, the expression levels of SOCS3 mRNA and protein in the SRNS group were significantly higher than those in the SSNS group (P<0.05).The expression of SOCS3 protein in children with PNS was positively correlated with 24hUTP, SCr and BUN (P<0.05), and negatively correlated with GFR (P<0.05). Conclusion There were differences in the expression of SOCS3 between children with SRNS and SSNS, and the differences were correlated with the changes of renal function indexes. These results suggest that the up-regulation of SOCS3 expression has a potential predictive value for GC resistance.