Abstract: Objective To study the mechanism of Shenkangwan (SKW) in treating early diabetic nephropathy (DN). Methods The effect of SKW on NO and transforming growth factor (TGF)-β1 production by the mesangial cells (MCs) of rats with early diabetic nephropathy was evaluated with serum pharmacological method. Results Compared with normal serum, the SKW-containing serum dose- and time-dependently inhibited TGF-β1 excretion and increased NO production in the MCs of rats with early DN (P<0.05 and P<0.01, respectively). Conclusion The therapeutic effect of SKW on early DN may rely on the balance modulation of cytokine network by increasing NO production and decreasing TGF-β1 excretion to prevent cytokine-induced damage of the MCs.