Increasing world population and vital need for protein sources, demands selection techniques for fast growing broilers to meet human needs. However, growth of important organs of these broilers does not match their growth rate. High growth rate increases metabolic activities and oxygen requirements that can lead to increased metabolic disorder. Since lungs can not provide enough oxygen for metabolic needs of these chickens, hypoxia occurs specially at high altitude and ascites syndrome can occur. This syndrome can cause significant economic loss to poultry industry. The aim of this study was to investigate cellular and molecular mechanisms of ascites syndrome. Heart samples were taken at weeks 2, 3, 4, 5 and 6 from 20 male broilers (Ross 308) that were kept at two different districts of sea level ( Rasht ) and 2150 meter above sea (Shahrekord). In Shahrekord feed restriction was exerted at week 4. Morphological and histopathological analysis (H E staining), collagen content measurements (OH proline measurement) and MMP level evaluation (gelatin zymography) were performed. Statistical analysis was carried out by GLM procedure from SAS. In Shahrekord's broilers, hypoxia caused increased MMP-2 levels in right ventricle wall that resulted in ECM degradation and heart remodeling that was evident in histological analysis. Also, there was a higher right ventricle volume in Shahrekord's samples as compared to that of Rasht . At week 4 there was lower levels of active MMP-2 in Shahrekord's samples that was followed by a significant increase in collagen content could be due to feed restriction at this week. Although broilers in Shahrekord district had a healthy appearance, low oxygen pressure had significant effect at cellular-molecular levels. However, by reversing these effects, feed restriction may have controlled onset of ascites syndrome in Shahrekord’s broilers.