Objective:To study the influence of miR-221 in theβcells of mice with diabetic nephropathy (DN), and to clarify the protective effect of miR-221 on DN.Methods:Twenty wild type C57BL/6J mice aged 8 weeks were divided into control group and DN group (n=10).The DN mice models were constructed with 14 weeks of high fat diet,and 100 mg·kg-1 streptozotocin (STZ)was used to induce the partial insulin deficiency.10 weeks later the blood glucose,serum creatinine,blood urea nitrogen content and 24h-urinary albumin excretion rate were detected.Theβcells of islet were isolated from the DN mice.The expression level of SOCS3 mRNA inβ cells of islet was valued by Real-time PCR.The proliferation of pancreaticβcells of islet was examined by MTT assay.The contents of insulin and insulin release levels in pancreaticβ cells of islet were detected by ELISA assay.Luciferase reporter gene assay was used to detect the luciferase reporter gene activity of SOCS3.Results:The DN mouse models were constructed successfully.The blood glucose,serum creatinine,blood urea nitrogen and 24h-urinary albumin excretion rate of the mice in DNA group were higher than those in control group (P < 0.05 ).After overexpression of miR-221,the expression level of SOCS3 mRNA in pancreaticβcells of islet and the proliferation ability ofβcells of islet of the mice in DN group were lower than those of normal islet cells (P < 0.05).Then luciferase reporter gene method found SOCS3 as one of the target genes of miR-221.After overexpression of miR-221,the insulin release level and insulin content in pancreaticβcells of islet were higher than those of normal islet cells (P <0.05).Conclusion:miR-221 can promopt the synthesis and secretion ofβ cells of islet and inhibit the dysfunction ofβcells of islet in the DN mice by down-regulating the SOCS3 level.