The link between dietary fat and coronary heart disease has attracted much attention since the effect of long-chain fatty acids on gene transcription has been established. The aim of this study was to investigate the effects of long-chain fatty acids and clofibrate on mRNA levels of specific lipid metabolism-related genes and to determine their effects on global transcriptome levels in a cardiovascular cell-line. After culturing P19CL6 cells with long-chain fatty acids or clofibrate, the expression levels of heart-type fatty-acid binding protein and peroxisome proliferators-activated receptors (PPARalpha,beta,gamma) were determined by reverse transcriptase-polymerase chain reaction. Additionally, global transcriptome profiles were compared using microarray analysis. Long-chain fatty acids significantly increased the abundance of PPAR and PPAR. Moreover, microarray analysis showed that the effects of linoleic and -linolenic acids, and clofibrate were similar but differed from those of palmitic and oleic acids. These findings show that cellular responses to polyunsaturated fatty acids differ from those observed with saturated and monounsaturated fatty acids.