Carotid bodies (CB) are the sensory organs to detect systemic hypoxia. CB respond instantaneously in few second requiring an initial transaction step involving O₂ sensor and changing protein content or activity. Chronic hypoxia stimulates cellular growth; metabolism and the regulation of genes encoding protein depends upon accurate sensing of PO₂ and activation HIF that is a key protein regulating cellular response to hypoxia. HIF regulates several genes including ET-1 and VEGF. It would be helpful to have an overview of the specific set of proteins present in the CB and the functions of such proteins in signal transduction and adaptation during hypoxia. Here, we present a first proteomic analysis of the rat CB preparation by comparison between normoxia and hypoxia. Proteomic investigation would be helpful to identify the stress-induced protein during hypoxia and aging. Two groups of adult Wistar rats, weighing 200–250 g were used. One was kept in room air (21% O₂) as a control group, the other was kept in a Plexiglas chamber for 12 days in chronic hypoxia (10–11% inspired oxygen). Exposure to hypoxia for 12 days produced a significant changes in expression protein providing an initial insight into the mechanism underlying differences in susceptibility to hypoxia at different age. Further investigation is needed to provide valuable biochemical information useful to elucidate the oxygen sensitive molecular mechanism.