The effect of dietary Echinacea purpurea (EP) on the response of zebrafish (Danio rerio) to a Flavobacterium columnare vaccine was investigated. Two hundred D. rerio with an average weight of 290 ± 40 g were selected and fed different levels of E. purpurea (5 g kg -1 diet -group 1, 10 g kg -1 diet -group 2, 20 g kg -1 diet -group 3, 30 g kg -1 diet -group 4, and 0 g kg -1 diet -group 5). Experimental feeding was begun 3 weeks prior to bath immunization and continued until the end of the experiment. Twenty-eight days after immunization the fish were challenged by bath immersion with F. columnare at a concentration of 1x106 CFU/ml. The relative percent survival of the experimental groups (1, 2, 3, 4 and 5) was 5.0, 6.0, 30.0, 36.0 and 5.0, respectively. In conclusion, diet supplementation with E. purpurea may effectively enhance the response of zebrafish to a F. columnare vaccine.