An unexpected finding was that MCT1b was expressed in the arterial capillaries but not the venous capillaries of the rete mirabile. This fact is incorporated into our model and helps to better explain. In the present study, we showed that spatially organized two lactate transporters facilitate O2 secretion from Root-effect hemoglobin by maintaining local blood pH low. We at first characterized the anatomical properties of the gas gland and rete mirabile in fugu swim bladder tissue at the light and electron microscopic levels. Those structures were well developed in the ventral wall, and we confirmed the presence of typical structures including basal labyrinth in gas gland cells and caveolae-like structures in Schizandrin-B endothelial cells of the rete mirabile. There are several advantages of using fugu for studying the mechanism of swim bladder O2 filling: its large size, well-developed gas gland and rete mirabile, and genome database availability. Similar studies are difficult to perform using small fish such as zebrafish or medaka. Pelster and Scheid Acipimox demonstrated that in gas gland tissue, the activity of enzymes involved in anaerobic glycolysis and the pentose phosphate shunt were as high as those in liver and white muscle, whereas the activity of enzymes responsible for oxidative metabolism in gas gland tissue was extremely low. As expected from previous studies that demonstrated the production of lactic acid in gas gland cells, we identified a monocarboxylate transporter, MCT4b, in the gas gland cells. MCT4b is thought to play a central role in the secretion of lactic acid from the gas gland cells to the blood vessels. On the other hand, it has been demonstrated, in cultured gas gland cells, that acid secretion was not inhibited by 1 mM cinnamate, an inhibitor of MCTs. At first, this fact seemed to contradict our conclusion that lactate is secreted by MCT4b. Nevertheless, our kinetic analyses indicated that MCT4b is a low-affinity, highcapacity transporter and is not inhibited by 1 mM cinnamate, eliminating the apparent discrepancy. The low-affinity, high-capacity property of MCT4b to lactic acid may prevent from saturation of efflux where the local lactic-acid concentration is high.