The present study aimed to investigate some hematological, histopathological and immunological parameters in the clam, Macoma edentula (Tellinidae) to serve as a reference for monitoring different environmental pollutants through the potential changes in the clam defence activities. Two localities at Lake Timsah, Ismailia exhibiting different levels of environmental contamination were selected for a comparative study of in vitro hemocyte activities. The results of DNA strand breakage in the Comet assay were expressed as the main tail DNA content and the mean tail length. The two measured parameters showed significant differences between the unpolluted and polluted samples. Water pollution was observed to cause significant histopathological changes in the mantle, gills and digestive gland of the tested clam, using light and electron microscopy. Histopathological changes of the mantle were represented in the arrangement of different cells vacuolation, swelling and distortion of gill filaments were also reported. The secretion of glandular cells increased in the polluted samples. Later on, such cells became completely necrotic and vacuolation was observed in most parts of the digestive gland cells. These results suggest that the use of such native bivalve in environmental biomonitoring can indicate the level of environmental pollutants including carcinogens in the examined animal model.