This study focussed on the complex regulation of lipid metabolism in the mammary gland of cows and the association between milk fatty acid (FA) profile and the expression of lipogenic genes in individual cows. Changes in FA profile were found to be accompanied by changes in the expression of regulatory genes related to a wide range of metabolic functions. Expression of most of key lipogenic genes and transcription factors such as peroxisome proliferator-activated receptor gamma (PPARG), and sterol regulatory element binding factor 1 (SREBP1) was mainly negatively correlated to the concentration of trans-FA and CLA isomers in milk. These correlations suggest that changes in ruminal lipid metabolism may result in modifications in the expression of lipid metabolism-related genes at mammary level.