Because Rhodiola plants are known to have a protective effect on diabetic nephropathy, this study aimed to investigate the inhibitory effect of salidroside, the main active component of Rhodiola plants, on high glucose-induced mesangial cell proliferation and its possible mechanism. Salidroside (1 approximately 100 microM) dose dependently inhibited high glucose-induced mesangial cell early proliferation. Exposure of mesangial cells to high glucose for 24 h significantly induced reactive oxygen species (ROS) accumulation, ERK1/2 phosphorylation, and p27 (Kip1) expression, and these changes were dramatically inhibited by salidroside in a dose-dependent manner. High glucose-promoted TGF- beta1 secretion was also significantly attenuated by treatment of mesangial cells with salidroside. These results indicated that salidroside had the ability to inhibit high glucose-induced mesangial cell proliferation, which is in correlation with salidroside suppressing TGF- beta1 production and ERK1/2 phosphorylation.