Abstract: AimTo study the mechanisms of anti-diabetic nephropathy of rhein on cultured human mesangial cells (HMCs). MethodsTo mimic the hyperglycemic (HG) environment of diabetic nephropathy, 30 mmol·L^-1 glucose were added to 10% FBS RPMI 1640. The HMCs were treated with rhein for 8, 24, 48 or 72 h, at these time, the bioactivity, total activity of transforming growth factor-beta₁(TGFβ₁), activity of p38MAPK (p38 mitogen-activated protein kinases, by using immunoprecipitate and Western blot), MMP-2 (matrix metalloproteinase-2), and MMP-9 (matrix metalloproteinase-9, by using gelatinase zymography) and the proliferation of HMCs in high glucose media were measured. Meanwhile the levels of secretion of FN in cultured HMCs were measured. ResultsThe results showed that rhein markedly inhibit the proliferation of HMCs, significantly reduce the bioactivity of TGFβ₁ and FN secretion in HMCs, and decrease the increased activity of p38MAPK, but showed no action on the activities of MMP-2 and MMP-9. ConclusionRhein reduced the secretion of FN and inhibited the proliferation of HMCs may through inhibiting the bioactivities of TGFβ₁ and p38MAPK.