Cardiac hypertrophy occurs in response to various stimuli including mechanical stress and is known as an independent risk factor for cardiac morbidity and mortality. Reactive oxygen species participate in signal transduction during cellular growth and differentiation. Although cellular redox balance may play an important role in cardiac hypertrophy and its regression, the mechanisms of regulation of redox genes are incompletely defined. Mechanical unloading in cardiac work leads to regression of cardiac hypertrophy and improvement of functional capacity of failing hearts. Therefore, understanding of the cellular responses and regulatory mechanisms to workload unloading is of clinical interest. We analyzed redox gene expression profiling in the rat model of cardiac hypertrophy-regression using cDNA microarrays and Westen blot analysis in order to evaluate the role of redox system in the genesis of cardiac hypertrophy and the regression of hypertrophy. Gene expression profiling was analyzed in the rat model of pressure overload induced cardiac hypertrophy and its regression. Cardiac hypertrophy was induced by the partial constriction of transverse aorta and regression (unloading) was achieved by relieving the constriction after significant cardiac hypertrophy had developed. At days 0, 1, 3, and 7 after pressure unloading, the left ventricles were extracted and subjected to gene profiling analysis using cDNA microarrays. Among 10,330 rat genes analyzed, 2,155 genes (20.8%) were up-regulated and 132 genes (1.3%) were down-regulated more than 2-fold during hypertrophy. Many of the redox genes such as thioredoxin, thioredoxin reductase 1 and 2, glutathione peroxidase, SOD, 8-oxoguanine-DNA-glycosylase, catalase were dynamically changed by the pressure overloading and unloading to LV. This study demonstrated the redox system may play an important role in the pathogenesis of pressure overload-induced LVH and its regression by unloading. Further studies should be followed to find out which redox gene is the most important or how to modulate the redox system to prevent progression of LVH to heart failure.