The effect of alkalinity (0, 2 and 4 g/L NaHCO3) stress on morphology of gill ionocytes in Nile Tilapia (Oreochromis niloticus) was studied by scanning electron microscopy, and four HCO3- transporters including carbonic anhydrase (CAⅡ, CAⅣ), Na+/HCO3- cotransporter (SLC4A4), and Cl-/HCO3- exchanger (SLC26A6) in gill, kidney and intestine were also observed by immunohistochemistry. The surface scanning of the gills showed that ionocytes cells were distributed close to the inter-lamellar regions of gill filaments (Fig. 1). According to the apical shape and size, the ionocytes cells could be divided into four subtypes, subtype Ⅰ, subtype Ⅱ, subtype Ⅲ and subtype Ⅳ (Fig. 2). The apical size of each subtype of ionocytes was positively correlated with the alkalinity stress strength, and the size of subtype Ⅲ cells was changed most obviously (P < 0.01) (Table 1); The ionocytes number increased significantly with the increase of alkalinity stress strength, and the number of subtype Ⅲ cells was increased most significantly (P < 0.01) (Table 1). The results of immunohistochemistry showed that CAⅡ, CAⅣ, SLC4A4 and SLC26A6 were expressed in gill and kidney of O. niloticus at fresh water and alkaline water (Fig. 3, Fig. 4). With the increase of alkalinity, the positive reactions became stronger (Table 2). However, no positive reaction was detected in intestinal at fresh water and alkaline water (Fig. 5). This result suggest that O. niloticus may change the quantity and morphological structure of ionocytes to adapt to alkaline environment, and that gill and kidney may play a key role in alkalinity regulation.