Somatostatins are a diverse group of peptide hormones known to regulate numerous growth, developmental, and metabolic processes in vertebrates. In this study, rainbow trout (Oncorhynchus mykiss) were used to investigate the role of somatostatins and their receptors in osmoregulation.  Fish were injected intraperitoneally with somatostain-14 (SS-14) or saline and transferred to 20% seawater (SW) and the levels of preprosomatostatin (PPSS) and somatostatin receptor (SSTRs) mRNAs in various tissues (e.g., gill, liver, pancreas) were determined by quantitative PCR. In gill, SW transfer had no effect on PPSS mRNA levels, but expression of SSTR 1A, 1B, and 2 increased; SS-14 inhibited SW-associated changes in SSTR expression.  mRNA levels of SSTR 1B in liver increased following transfer SW; SS-14 injection prevented the SW-associated increase in SSTR 1B and increased the expression of SSTR 2. In pancreas, SW transfer significantly increased PPSS II’ mRNA levels, which were attenuated by SS-14, but there was no significant effect on the expression of SSTRs. These results indicate that exposure to SW stimulates the expression of PPSSs and SSTRs in a tissue- and variant/subtype-specific manner.  Such a role of the somatostatin signaling system in SW adaptation broadens our knowledge of the actions of somatostatin in vertebrates.