Abstract： Objective To explore the effect of P38 mitogen-activated protein kinase(P38MAPK)on diabetic nephropathy(DN)and the mechanism of simvastatin-prevented development of DN.Methods Rat mesangial cells(RMC)were incubated with high glucose(HG),advanced glycosylation end products(AGE)or H2O2 with or without pre-treatment with SB203580(P38MAPK specific inhibitor)or simvastatin(SI).The expressions of pho-P38MAPK,monocyte chemoattractant protein-1(MCP-1)and intercellular adhesion molecule-1(ICAM-1)in MC were detected by Western-blot or RT-PCR.Results HG,AGE or H2O2 were able to activate P38MAPK and increase the expressions of MCP-1 and ICAM-1 in RMC.The expressions of MCP-1 and ICAM-1 were inhibited by SB203580.SI inhibited the activation of P38MAPK and reduced the expressions of MCP-1 and ICAM-1.Conclusions P38MAPK is an upstream signaling molecule of MCP-1 and ICAM-1.P38MAPK may be one of the initiating signals of DN.SI can inhibit the expressions of MCP-1 and ICAM-1 by repressing P38MAPK signaling pathway and therefore prevent the development of DN