In order to study the biological control methods of fish furunculosis, actinomycete I6 strain with strong antagonistic activity was screened from soil by using the fish furunculosis pathoge Aeromonas salmonicida as indicator strain. 16S rRNA analysis indicates that it is a Streptomyces sp. strain. The secondary metabolites produced by I6 exhibit strong antibacterial activity to A. salmonicida in vitro, and no obvious adverse effect on fish was observed. This result provides a reference for the treatment and prevention of A. salmonicida. In order to enhance the yield of the antibacterial active substance of I6, the fermentation conditions of the I6 strain were optimized. The results showed that the optimal fermentation medium is determined to be AM3-1 with initial pH of 7～8, and the optimal cultivation time is 5 days. The optimum bacterial age for seed liquid is 36 h. All these results shows that I6 has a significant inhibitory effect on the growth of fish furunculosis pathogen A. salmonicida, and has potential development and application value in fishery biocontrol.