The association of cardiac disorder induced by hypoxia with obesity was reported. To explore the cardiac hypertrophy and apoptosis in obese Zucker Rat exposed to intermittent hypoxia, obese or lean Zucker rats were separated into hypoxia (12% O2, 88% N2 ) or normoxia (20% O2, 80% N2) groups (n=6 ) with 8-hour-exposure per day for 7 days. The myocardial morphology, apoptosis and hypotrophy- related pathway components were measured by histological, western blotting or RT-PCR analysis. The data show significantly increased activities of IL-6-MEK-5-ERK5 hypertrophic pathway, and FAS- and mitochondria-dependent apoptotic pathway in hypoxia-exposed lean rat hearts, compared with normoxia-exposed lean rat group. Under normoxia condition, compared with lean rat hearts, increased activity also appeared in obese rat hearts. This increase was further enhanced by hypoxia- exposure in obese rat hearts, compared with either lean hypoxia group or obese normoxia group. Taken together, the detrimental effects induced by hypoxia or obesity were further enhanced when these two factors were combined, resulting from the increased activities of IL-6-MEK-5-ERK5 signaling and both FAS- and mitochondria- dependent apoptotic pathways.