H-P-I axis plays a critical role in the fish stress response.It is regulated by a series of factors.Cadmium is one of the most toxic heavy metals in the world, however, its effects on the teleosts H-P-I was largely unknown.Here we investigated the effects of waterborne cadmium exposure on the secretion and synthesis of hormones in H-P-I axis, analyzed the expression of glucocorticoid receptors (GR), and two GR regulators, FKBP5 and NCoR1.Data showed that cadmium only disrupts the secretion and synthesis of cortisol, but affects neither the hormones at H or P level nor the expressions of their receptors (CRHR, MC2R).StAR, CYP11A1, CYP11B1 which encoded the key enzymes in the cortisol synthesis pathway were significantly up-regulated in the kidney (containing head kidney), 11bHSD2, required for the conversion of cortisol to cortisone, was raised in the kidney, intestine, brain, and hepatopancreas, while the gene 11bHSD2 encoding for the reverse conversion enzyme was increased at gill and almost unchanged in other tissues.GR was declined in the intestine, gill and muscle, and the key GR regulator, FKBP5 was up-regulated at the GR-decreased tissues, however, NCoR1 was almost unaltered.Thus we supposed that GR, FKBP5 and 11bHSD2 were involved in the cadmium induced cortisol disruption.