Exercise has various beneficial effects on liver function, enhancing both nutrient metabolism and antioxidant capacity. To explore the molecular mechanisms underlying these changes, we used a high-density cDNA microarray containing probe sets for 2,845 genes to analyze changes of gene transcription in the livers of rats after 4 weeks of running exercise. In comparison with sedentary animals, 105 genes were up-regulated and 86 genes were down-regulated, including genes with unknown functions. In addition, we detected an increase of p38 mitogen-activated protein kinase and protein and of the protein for signal transducer and activator of transcription 3 (stat3), corresponding to the increase of these mRNAs shown by microarray analysis. These results indicate that long-term exercise can alter liver function via changes of gene expression, especially the genes encoding signal transduction proteins such as p38 and stat3.