Objective To observe the effect of mammalian target of rapamycin(mTOR)pathway blocker on CD4⁺CD25^highTreg in diabetic nephropathy(DN)rats, and to explore the possible mechanism of Regulatory T cell(Treg)in DN. Methods DN rats were randomly divided into model group(group B), FK506 intervention group(group C), and ku0063794 intervention group(group D), with normal rats as Control(Group A). Renal pathology, mTOR, Raptor, Rictor of renal tissue, serum interleukin-17(IL-17), transforming growth factor-β1(TGF-β1), and blood CD4⁺CD25^highTreg were detected at 4th and 8th weeks. Results(1)mTOR, Raptor and Rictor in group B were significantly higher than those in group A at the 4th and 8th weeks(P<0.05). The mTOR in group C decreased at 4th week, which was lower than that in the group B(P<0.05). mTOR in groups C and D were lower than that in group B at 8th week(P<0.001). The Raptor in groups C and D were lower than that in B group at 4th and 8th weeks(P<0.05). The Rictor of the two groups(C and D)was lower than that of B group at 4th week(P<0.05). After 8 weeks, there was no difference in Rictor between groups C and D.(2)CD4⁺CD25^highTreg in group B was significantly lower than that in group A at 4th and 8th weeks(P<0.05). CD4⁺CD25^highTreg in groups C and D gradually recovered after 4 weeks, higher than in group B(P<0.05); and it further increased at 8th week, higher than that at 4th week(P<0.05); There was no difference between groups C and D.(3)Pathological scores of the groups C and D were lower than that of group B(P<0.05). There was no difference between the groups C and D.(4)Serum TGF-β1 and IL-17 in group B were higher than those in group A at 4th and 8th weeks(P<0.05), and they decreased after intervention(P<0.05). TGF-β1 in group C was lower than that in group D at 4th and 8th weeks(P<0.05).(5)At 8th week, Rictor was negatively correlated with CD4⁺CD25^high Treg(P<0.05), and positively correlated with TGF-β1, IL-17, and pathological scores(P<0.05). Raptor was positively correlated with pathological scores(P<0.05), and there was no correlation with CD4⁺CD25^high Treg, TGF-β1, or IL-17(P>0.05). Conclusion CD4⁺CD25^highTreg may be regulated by the Rictor-mTOR pathway and participate in the pathogenesis of diabetic nephropathy.