Fish are exposed to endocrine-disrupting chemicals (EDC), which are well known to disturb not only the reproductive system but also the immune system in vertebrates. However, the mechanisms by which these compounds are able to modify fish immunity are not well understood. In order to test the EE2 effects on immunity in selected organs, we exposed rainbow trout male juveniles for 3 weeks to EE2 concentrations ranging from 0.01 to 1. μg/L. The results of this study suggest that EE2 affects the immunity of rainbow trout in a tissue dependent manner. This molecule affects both cellular and humoral immune systems. Indeed, blood leukocyte populations, as well as hepatic and plasma lysozyme, plasma MPO and renal complement activities, are modulated by EE2. Moreover, EE2 alters the gene expression of some mucus compounds, hepatic expression of complement sub-unit and lysozyme, or genes involved in the hepatic phagocytosis and transport of immunoglobulin across the liver.