Diabetes mellitus is an important risk factor of atherosclerosis. Although the mechanism for accelerated atherosclerotic disease in diabetes mellitus is not clear, extracellular matrix formation by vascular smooth muscle cells has been accepted to play important roles during development of atherosclerosis. High glucose condition has been reported to increase the synthesis of extracellular matrix such as collagen and fibronectin in cultured mesangial cells, implicating high glucose for the development of diabetic nephropathy. We studied here the effect of high glucose on the synthesis and gene expression of collagen and fibronectin in vascular smooth muscle cells. We found that vascular smooth muscle cells grown in high glucose (25 mM) medium for 1, 2, and 3 days synthesized more collagen and noncollagen protein, as compared to the cells grown in normal glucose (5.5 mM) medium for the same periods of time. We also found that cells grown in high glucose for 1, 2, and 3 days expressed higher level of type 1 procollagen mRNA than that of the cells grown in normal glucose. There was, however, no difference in the amount of newly synthesized fibronectin between cells grown in normal and high glucose condition. These results suggest hyperglycemic condition in diabetes may accelerate the atherosclerotic process by stimu-lating vascular smooth muscle cells to produce more collagen. K e y w o r d s : vascular smooth muscle cell, collagen, fibronectin, high glucose, diabetes mellitus, atherosclerosis