Aim To observe the effect of total flavonoid from Mori folium(TFMF) on renal interstitial fibrosis in type 1 diabetic mice and its possible mechanism.Methods Diabetic mice were induced by intraperitoneal injection of streptozotocin(STZ) dissolved in 0.01 mol·L-1 citrate buffer(pH 4.5) at 150 mg·kg-1 body weight after 12 h of food deprivation.Forty model mice were divided randomly into four groups: model group, and low-(0.25 g·kg-1), moderate-(0.5 g·kg-1), high-dose groups(1 g·kg-1) fed with TFMF once daily.In addition, eight normal mice were used as normal group.After 12 weeks, the fasting blood glucose(FBG), serum creatinine(Cr), blood urea nitrogen(BUN) and microalbuminuria(mAlb) were measured.Masson staining, Sirius red staining and collagen type Ⅳ immunohistochemical staining were used to detect the expression of collagen protein in the cortex, while laminin staining to assess the degree of glomerular and renal tubular basement membrane thickening.The protein expressions related to epithelial-mesenchymal transition and PI3K/Akt/mTOR in the renal cortex of mice were detected by Western blot.Results The moderate and high dose of TFMF could significantly decrease the levels of FBG, Cr, BUN and mAlb in diabetic mice, meanwhile decreasing the expression of α-SMA protein by inhibiting the activation of PI3K/Akt/mTOR signaling pathway, which led to the amelioration of the pathological alterations of renal tissue.Conclusions The moderate and high dose of TFMF can reduce the level of renal interstitial fibrosis in type 1 diabetic mice, and its mechanism may be related to the inhibition of activation of PI3K/Akt/mTOR signaling pathway.