Prostaglandin E2 (PGE2) is an important lipid mediator that plays diverse functions in mammals. Four receptor subtypes of PGE2, designated EP1-4, have been identified to mediate its signaling pathways. Extensive studies of PGE2 and its receptors have been carried out in mammals, but little is known in fish, including Atlantic salmon. In the current study, the distribution of Atlantic salmon EP4 receptor in different tissues was investigated using RT- and real-time PCR. A custom made antibody was used to investigate the distribution of this receptor in different tissues. Quantitative analysis by real-time PCR revealed that the expression was more abundant in the spleen followed by head kidney, skin and fin while it was least expressed in heart, muscles and brain. The staining intensity obtained by immunohistochemistry correlated with the RT-PCR results. EP4 expression was strongly associated with the immune cells in different tissues. To our knowledge, this is the first study to describe the distribution of EP4 receptor in Atlantic salmon tissues. Our findings suggest that EP4 may play a role in mediating immune responses as observed in mammals.