The present study aimed to investigate the characteristics in gill histology and ultrastructure of flathead grey mullet, Mugil cephalus; as well as to compare between these structures in fish specimens inhabiting waters with different salinities. Fish specimens of M. cephalus were collected from Great bitter Lake at Ismailia Governorate (salinity: 38-45‰) and Bardawil Lagoon at Al-Arish, North Sinai Governorate (Salinity: 64-68 ‰). Histological examination showed that the chloride cells in gills of M. cephalus inhabiting marine waters (Great Bitter Lake) are located within the epithelium of the inter-lamellar regions and secondary lamellae; but in hypersaline waters (Bardawil Lagoon) fishes, chloride cells are located only within the primary epithelium of the inter-lamellar regions. The flat elongated pavement cells of secondary lamellar epithelium in marine fishes are more flattened than that in hypersaline water fishes. In each epithelium of the two opposite sides of secondary lamellae, two layers of cells were observed in hypersaline specimens, in which they overlap and interdigitate in a complex manner; but in marine specimens, only one layer of pavement cells was observed. The ultrastructure examination showed that chloride cells in specimens of marine water are large; ovoid or rounded in shape with a rich population of mitochondria. While, chloride cells in fishes inhabited hypersaline water displayed more rich populations of mitochondria. In the present study, statistical analysis to gill morphometric characteristic counts and measurements of gills in M. cephalus inhabiting marine water and hypersaline water revealed that there are statistically significant differences between these groups for most counts and measurements as well as their ratios.