Hypoxia is a crucial physiological stimulus in development and plays a key role in the pathophysiology of cancer, stroke, pulmonary disease, and other major causes of mortality (Iyer et al., 1998). Responses to changes in oxygen concentrations are primarily regulated by hypoxia inducible factors (HIFs). HIFs are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of oxygen-regulated and a constitutive non oxygen-regulated subunits and are belonged to the basic helix-loop-helix-PAS (bHLH-PAS) superfamily (Bruick, 2003). In mammals, three genes have been shown to encode HIFsubunits namely HIF-1 , -2 and -3 . The HIF-1 protein is more widely expressed, while its homologs, HIF2 /Endothelial PAS domain protein (EPAS-1) (Tian et al., 1997) and HIF-3 (Gu et al., 1998) are tissue and developmental specific in their expression. HIF1 is expressed in the brain, heart, lung (Jain et al., 1998) and also in the carotid body (CB) (Baby et al., 2003; Tipoe and Fung, 2003). Whereas HIF-2 is expressed in the endothelial cells of various tissues, such as brain, heart, and liver, and the mRNA is also observed in alveolar epithelial cells in the lung (Ema et al., 1997). The EPAS-1 expression in mice embryo was induced by hypoxia for proper cardiac function (Tian et al., 1998). Furthermore, all the HIFsubunits have been found in the kidney where diverse functions of the three had been shown. HIF-1 and -2 activate the expression of the HIF-mediated gene such as erythropoietin (EPO), whereas HIF-3 is likely an inhibitor of EPO gene transcription (Hara et al., 2001; Jelkmann, 2004). HIF activates transcription of genes that increase systemic oxygen delivery or provide cellular metabolic adaptation under conditions of hypoxia. Abnormal HIF expression is related to numerous diseases of the vascular system, including heart disease, cancer and chronic obstructive pulmonary disease (Covello and Simon, 2004). The expression of HIF-1 subunit in the rat CB plays an essential role in the transcriptional regulation of the structural remodeling and functional modulation of the organ in chronic hypoxia (CH) (Fung, 2003). However, less is known about the expression and function of HIF-2 and HIF-3 in the rat CB. The aim of the present study was to examine the mRNA and protein expression of HIF-2 and -3 in the CB of rats in normoxia and in CH breathing 10% O2 in isobaric chamber for up to 4 weeks.