Objective:To observe the effect of spironolactone on oxidative stress of glomerular mesangial cells induced by high glucose,and explore whether the MAPKs family signaling pathway was involved in this effect. Methods:DHE fluorescence staining was used to evaluate the intracellular production of reactive oxygen species(ROS),NBT kit was used to detect the intracellular SOD activity,and Western blot was applied to identify the phosphorylated and total protein expression of MAPKs family genes,such as ERK,JNK and p38MAPK in cultured human mesangial cells (HMC) treated with high glucose or spironolactone. Results:DHE fluorescence staining showed that the production of ROS in HMC was markedly increased with the treatment of high glucose,while which was significantly decreased in the stimulation of spironolactone. Compared to the treatment of high glucose,intracellular SOD activity was significantly increased(P < 0.05) with the treatment of spironolactone. Western blot analysis suggested that the high sugar significantly increased the expression of phosphorylation of ERK and p38MAPK in HMC cells,while given the treatment of spironolactone,these effects were reversed(P < 0.05). Furthermore,there were no remarkable differences among the groups in phosphorylated JNK,total protein level of ERK,p38MAPK,and JNK. Conclusion:Spironolactone may play a role in reducing the production of intracellular ROS and increasing the activity of SOD and antagonism of oxidative stress induced by high glucose via down-regulation of the phosphorylation level of MAPK family signaling. All these actions may contribute to the protection of the glomerular mesangial cells and postponement of kidney glomerulus sclerosis.