The activities and expression of protein kinase C isoenzymes were examined in glomerular mesangial cells cultured under high glucose conditions. Exposure of cells to high glucose concentrations (27.8 mmol/l) for more than 3 days resulted in a significant elevation of protein kinase C activities in the membrane fraction. Of the protein kinase C isoenzymes, the levels of protein kinase C alpha significantly increased in the membrane fraction after 3 days of exposure to glucose, and protein kinase C zeta increased after 5 days of exposure. Levels of protein kinase C delta and epsilon remained unchanged and protein kinase, C beta and gamma were not detected. These results indicate that protein kinase C alpha and zeta are translocated under high glucose conditions possibly through different mechanisms.