Abstract: To determine the effects of Fibrous root of Coptis chinensis Franch (FRC) and berberine (BBR) on non-specific immunity and disease resistance against Aeromonas hydrophila infection in grass carp (Ctenopharyngodon idella), fish were fed with diets containing 1.00%, 0.50%, 0.25%, 0.10%, 0.00% of FRC powder and 0.05% of BBR for 28 days. Fish were challenged with A. hydrophila 28 days post feeding and survival rate (SR) was recorded over 14 days post challenge. Nitroblue tetrazolium (NBT) activity, serum lysozyme activity, phagocytic activity and complement C3 level were studied to assess the immune response of fish. The results revealed that dietary FRC and BBR increase the NBT activity, serum lysozyme activity, phagocytic activity and complement C3 level in grass carp when compared to the model group (MD). Feed containing 0.50% FRC was the most effective with the SR of the fish significantly increased by 44% compared to MD. The in vitro antibacterial activity of FRC and BBR were investigated with the minimum inhibitory concentration (MIC) method and showed strong inhibitory effects. The results indicated that FRC and BBR can be used as immunostimulants to enhance the non-specific immunity and disease resistance of grass carp against A. hydrophila.