Reducing the reliance on fishery by-products as amino acid and fatty acid sources in feeds for farmed fish is a major objective today. We evaluated the effect of dietary fish oil or dietary fishmeal replacement by vegetable oils and plant proteins respectively through analysis of hepatic transcriptomes in rainbow trout (Oncorhynchus mykiss). Fish were fed right from first feeding with diets based on plant by-products before being killed. We analysed the hepatic gene profile using trout cDNA microarrays (9K). Our data showed that seventy-one and seventy-five genes were affected after fish oil and fishmeal replacement respectively. The major part of modified gene expression coding for proteins of the metabolic pathways was as follows: (i) a lower level of expression for genes of energy metabolism found in fish after fishmeal and fish oil replacement; (ii) a lower level of gene expression for fatty acid metabolism (biosynthesis) in fish fed with vegetable oils; (iii) a differential expression of actors of detoxification metabolism in trout fed with vegetable oils; (iv) a lower level of expression of genes involved in protein metabolism in fish fed with plant proteins. Overall, our data suggest that dietary fish oil replacement is linked to a decreased capacity of fatty acid biosynthesis (fatty acid synthase) and variation of detoxification metabolism (cytochrome P450s) whereas dietary fishmeal replacement may depress protein metabolism in the liver as reflected by glutamine synthetase.