Objective To observe the changes in the expression of RANK/RANKL in rat kidney treated by tripterygium wilfordii polyglucosides (TWP) in STZ induced type 2 diabetic kidney disease (DKD) and to explore its possible renoprotective mechanism.Methods T2DM animal model was established by high glucose and high fat diet plus intraperitoneal injection of STZ.The modeled rats were randomly divided into DKD group(DKD,n=8) and TWP treatment group(DT,n=8).Normal rats were taken as control group(NC,n=8).DT rats were lavaged with TWP in a dose of 50 mg/kg · d,while the NC group and DKD group were lavaged with equal volume of normal saline every day.The indicators of FPG,FIns,UAlb,BUN,Scr,and Ucr were measured before and after 12-week intervention.PAS staining was used to evaluate the pathological change of the kidney.Immunohistochemistry and Western-blot were used to observe the protein expressions of RANK,RANKL,and nephrin.Results Compared with NC group,kidney pathological changes of DN group were aggravated with higher levels of FPG,UAlb,Ccr and BUN at 12th week.The expressions of RANK[(0.27±0.05) vs (0.68±0.11)] and RANKL[(0.23± 0.07) vs (0.62±0.08)] were prominently increased in kidney in DN group than those in NC group,while the expressions of nephrin were decreased(P＜0.01).Compared with DKD group,the above indexes and renal pathological changes were improved in DT group.The expressions of RANK[(0.45 ± 0.09) vs (0.68±0.11)],and RANKL[(0.39±0.06) vs(0.62±0.08)],were markedly inhibited in DT group,while nephrin expressions were increased(P＜0.01).Conclusion TWP can protect the kidney in rats with DKD by inhibiting the expression of RANK/RANKL.