The present study was designed to evaluate replacing solvent-extracted soybean meal (SBM) with solvent-extracted cottonseed meal (CSM),affected fish growth and health of juvenile grass carp in an 8-week trial.To evaluate the health impact,selected stress-and immune-response biomarkers were quantified at enzyme activity and the gene transcript (mRNA) level.Four diets containing 0%,16.6%,32.7.0% and 48.9% CSM as replacements of 0%,35%,68% and 100% of SBM on an equal nitrogen basis (containing ~35% crude protein)were fed to grass carp (initial body weight 7.14±0.75 g fish-1) in triplicate aquaria twice daily to apparent satiation for subsequent determination of growth response,hematology,expression and activities of antioxidant enzymes.The results indicated that the CSM could replace 35% SBM in diets for juvenile grass carp.Fish fed diet containing 16.6% CSM as a replacement of 35% of SBM were not affected weight gain (WG),feed efficiency ratio (FER) and feed conversion ratio (FCR) (P>0.05),but significantly decreased WG,and PER and increased FCR(P<0.05) as the replacement up to 68%.Values for red blood cell count (RBC),hematocrit (Ht) and hemoglobin (Hb) were significantly affected by dietary levels of CSM.Fish fed diet containing 16.6% CSM as a replacement of 35% of SBM had significantly improved Ht and Hb(P<0.05),but total replacement of SBM by 48.9% CSM significantly decreased RBC,Ht,Hb (P<0.05).There were diet-related differences in expressionand activities of antioxidant enzymes.The enzyme activities of CAT,GSH-Px and total SOD were significantly increased (P<0.05) when dietary level of CSM were improved from 16.6% to 48.9%.And the activities of enzymes of fish fed the highest levels of dietary CSM were simiilar to the control.The content of MDA were also significantly increased as the replacement of SBM with CSM increased from 35 to 100%.When total replacement of SBM by 48.9% CSM,an increase in GPx and CAT mRNA parallels the increase in the activities of the enzymes compared with low CSM groups(CSM35); However,an increase in Cu-Zn SOD gene expression (in group CSM35) in contrast to a decrease in enzyme activity suggests a role for post-translational modification in altering the activity of Cu-Zn SOD.This results indicates that juvenile grass carp was sensitive to gossypol toxicity in CSM or nutrition factor in SBM.Gossypol or other compounds present in high proportion of CSM or SBM in diet may result in fish were in oxidative stress status by improving the activity or changing gene expression of antioxidant enzymes.In conclusion,juvenile gras..s carp fed diets containing high level CSM(32.7.0% and 48.9%) as replacements of SBM showed some changes in growth,hematology,gene expression and activities of antioxidant enzymes.