The objective of this study was to elucidate the in vivo effects of the ethanol extract of wooly Glycine tomentella Hayata (GTE) root on tilapia to elucidate whether GTE has antistress activity. Tilapia as an animal model were fed with or without GTE, then injected with lipopolysaccharide (LPS) or ammonium chloride (NH(4)Cl). The tilapia were exposed to 100 mg/L of aqueous NH(4)Cl, and/or acute cold stress. Growth parameters of the tilapia were measured during the feeding trials. Tilapia injected with GTE (20 μg/g of fish), NH(4)Cl (100 μg/g of fish) and/or LPS (1 μg/g of fish) were then sampled 2 h poststimulation. GTE significantly inhibited cyclooxygenase-2 expression and hemoglobin (Hb) dimer formation (36 kDa). GTE also improved growth and blood viscosity and upregulated eicosapentaenoic acid content of erythrocytes. The in vivo results indicated that GTE (20 μg/g of fish) can be applied as a stress-tolerance enhancing agent for the aquaculture industry.