Infiltration of circulating monocytes into glomeruli has been implicated in the pathogenesis of glomerular injury in many human and experimental forms of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1), a potent chemokine with considerable specificity for monocytes, can be up-regulated by various cytokines and growth factors in mesangial cells. Glomerular infiltration of monocytes has been reported in diabetic nephropathy as well. However, effect of high glucose on MCP-1 expression in human mesangial cells has not been known well. We investigated the effect of high glucose on MCP-1 expression and its signal transduction pathway. Human mesangial cells were conditioned with glucose(5-60 mM) or mannitol chronically for up to 5 days. Expression of MCP-1 mRNA and protein was measured by Northern blot analysis and ELISA respectively. To examine the role of transcription factor AP-1 or NF-KB, electrophoretic mobility shift assay(EMSA) was performed. Glucose induced MCP-1 mRNA expression in a time and dose dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. EMSA revealed that glucose increased the AP-1 binding activity in a time and dose dependent manner but not NF-B. Inhibitor of AP-1, curcumin(7.5- 15 muM) dose dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein(12.5-50 muM) and herbimycin A(0.1-1 muM) inhibited the high glucose-induced MCP-1 mRNA expression in a dose dependent manner and also suppressed the high glucose-induced AP-1 binding activity. In summary, high glucose induces mesangial MCP-1 expression partly via tyrosine kinase-AP-1 pathway.