Agrimonia pilosa is rich in polyphenol compounds such as flavonoids and has broad antibacterial activity. This project, therefore, evaluated the antibacterial activity of A. pilosa extract against Photobacterium damselae in vitro and on immunity and disease resistances against P. damselae in Eleutheronema tetradactylum. The results showed that A. pilosa extract has antibacterial activity against P. damselae in vitro and if the E. tetradactylum was fed with A. pilosa extract at levels of 0, 1, 2, 3 and 4% in feed for 28 days the weight gain, Mx expression in kidney, SOD and lysozyme activities in serum of fish showed a significant increase (p<0.01) in 3 and 4% added groups of A. pilosa extract. Besides, E. tetradactylum was fed with A. pilosa extract at levels of 0, 2, 3 and 4% in feed for 28 days then challenged with P. damselae, the disease resistances of all added groups were significantly better than the control group (p<0.01) with the best protective abilities increased by more than 60% in 3 and 4% added groups of A. pilosa extract.