Tanshinone ⅡA (TⅡA) is widely used for the treatment of a number human diseases, including diabetic nephropathy (DN) (1). The present study was performed to examine the role of the transforming growth factor β (TGFβ)/p65 pathway under TⅡA treatment in a glomerular mesangial cell model of DN. Firstly, it was identified that TⅡA inhibited the proliferation of HBZY‑1 cells, while simultaneously suppressing the expression of TGFβ and p65. In addition, glucose-induced HBZY‑1 cells were treated with TⅡA, si‑TGFβ and si‑p65. The results revealed that si‑TGFβ or si‑p65 were able to inhibit the proliferation of HBZY‑1 cells as well. Finally, the expression of TGFβ and p65 in a rat model of DN treated with TⅡA was detected. The results demonstrated that renal hypertrophy and 24 h urinary protein excretion were ameliorated in TⅡA-treated rats with DN. Furthermore, it was revealed that the protein levels of TGFβ and p65 were decreased in the DN rats following TⅡA treatment. In conclusion, the present study demonstrated that TGFβ and p65 were activated by TⅡA in HBZY‑1 cells. In addition, the expression of TGFβ and of p65 was downregulated in rats with DN treated with TⅡA.