Cytokine responses, non-specific immune activity and growth promotion effect of dietary caper (Capparis spinosa) supplementation were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout (12.04 ± 0.71 g) were fed diets containing three doses of caper methanolic extract [0 (Control), 0.1 and 0.5 g kg−1 of feed] for 30 days. At the end of the feeding trial, expression levels of cytokine genes that included IL-1β, IL-8, TGF-β, IL-12p40, TNF-α1 and IL-10 in head kidney was analyzed using qRT-PCR, and blood and serum were collected to determine superoxide anion production (SAP), phagocytic, lysozyme and myeloperoxidase activities. Expression levels of all cytokines, except TNF-α1 were elevated in the 0.1 g kg−1 caper extract fed fish group compared to other groups. In 0.5 g kg−1 caper extract treated fish, only IL-12p40 and IL-10 genes were up-regulated compared to control group fish. SAP was increased in both caper extract treated groups compared to the control, and the highest level was observed in the 0.1 g kg−1 group. Phagocytic activity in both the caper extract treated groups was increased compared to control with no differences observed between those groups. Lysozyme and myeloperoxidase activities were recorded to be the highest in the 0.1 g kg−1 fed fish group compared to other groups. Growth promotion was affected positively when caper doses were increased. Survival rate was significantly higher in 0.1 and 0.5 g kg−1 caper extract treated fish groups compared to control (P < 0.05) after challenged with Aeromonas hydrophila. These results indicate that caper extract stimulates innate immunity through cytokine-mediated responses and promote growth in rainbow trout.