In the present study, transcript profiling was carried out in liver biopsies from high-yielding dairy cows at week 5 of lactation in order to identify genes and pathways regulated by feeding rumen-protected conjugated linoleic acid (CLA) during the transition period. Analysis of a bovine whole genome microarray revealed a total number of 130 ... annotated differentially expressed genes (DEGs) in the liver between cows of the CLA group and the control group (filter: P < 0.05 and fold change (FC) = 1.3 or =- 1.3). The number of DEGs in the liver being up-regulated was markedly higher than that being down-regulated (86 vs. 44). Gene set enrichment analysis revealed that the most enriched biological processes and molecular functions assigned to the 86 up-regulated genes were S-methyltransferase activity, ribonucleoprotein complex biogenesis, homocysteine S-methyltransferase activity, methionine biosynthetic process and spliceosome assembly, while the most enriched biological processes and molecular functions assigned to the 44 down-regulated genes were exopeptidase activity, cytokinesis after mitosis, cytokinesis during cell cycle, protein serine/threonine kinase activity and cytokinesis. The microarray dataset from this study has been deposited in NCBI´s Gene Expression Omnibus under the accession number GSE87391.