To understand the acclimation strategies of red tilapia to different environments, this study aimed to evaluate different responses of red tilapia (O. mossambicus × O. niloticus) to salinity (10-30‰), alkalinity (1-3 gL-1 NaHCO3) and salinity and alkalinity (10/1-30/3 ‰/gL-1NaHCO3) environments. Localization, type, size, and numeration of gill ionocytes were investigated on the same specimens by scanning electron microscopy (SEM) and immunohistochemistry (IHC) with antibodies of Na+/K+-ATPase (NKA), Na+/K+/2Cl-contransporter (NKCC), cystic fibrosis transmembrane conductance regulator (CFTR) and carbonic anhydrase (CA). Ionocytes were only located on filaments conducted by SEM. Four types of ionocytes namely pit, convex, concave and transitory types were determined morphologically by their apical openings of which concave and transitory type were not present in freshwater (FW) and saltwater (SW) fish (10). Both ionocytes size and number increased with elevated stress levels. In comparison to FW, density of ionotypes increased to about 4.75, 3.00 and 3.44 fold in SW (30), AW (3) and S&AW (30/3) respectively. Immunoreactive cells on gill filaments confirmed branchial distribution of ionocytes. Immunoreaction of NKA, NKCC and CA appeared in FW except for CFTR while they all appeared in SW (30), AW (3) and S&AW (30/3).