This study investigated the early expression of T-cell markers and genes potentially involved in the induction of soybean meal (SBM) enteropathy in the distal intestine (DI) of Atlantic salmon (Salmo salar L.). Quantitative PCR was used to study the expression of CD3, CD8beta, transforming growth factor beta (TGF-beta), interferon-gamma-inducible lysosomal thiol reductase (GILT) and interleukin-1beta (IL-1beta) in salmon fed SBM for 1, 3 and 7 days using fish fed fishmeal as controls. In the same tissue, the morphological development of SBM enteropathy was evaluated by routine histology and the presence of T cells was mapped by immunohistochemistry. TGF-beta was significantly down-regulated on all days of feeding SBM. GILT was significantly down-regulated on days 3 and 7 compared to day 1. A depression in the expression of T-cell markers was observed on day 3 whereas increased densities of T cells were observed at the base of mucosal folds after 7 days of feeding SBM. Down-regulation of GILT and TGF-beta may lead to sensitization of intraepithelial lymphocytes and failure to maintain normal mucosal integrity in the DI. These responses are implicated in the pathogenesis of SBM enteropathy in Atlantic salmon.