Abstract: The anti-inflammatory activities and mechanisms of phenolic compounds from Sargassum fusiforme(SFPC)were studied in lipopolysaccharides(LPS)-induced zebrafish model. The optimal LPS-induced inflammatory model in zebrafish was established,and the anti-inflammatory activities of SFPC with different concentrations were investigated by determination of yolk sac size,heart-beating rate,NO production rate,cell death rate and reactive oxygen(ROS)production rate. The results showed that SFPC(50,100,200 μg/mL)had a protective effect on inflammation induced by LPS(8 μg/mL)in a dose-dependent manner. The optimal concentration of 200 μg/mL SFPC significantly reduced the heart-beating rate(102.56%,P<0.05)and yolk sac size(109.18%,P<0.05). The rates of NO production,cell death and ROS production decreased from 202.48%,168.45% and 353.44% to 75.62%,101.25% and 128.91%,respectively. In this study,the zebrafish model was used for the first time to reveal the anti-inflammatory activity of SFPC in vivo. This study provides a theoretical basis for the application of SFPC as anti-inflammatory agent in functional food and cosmetics.