The current situation of rising demand for animal products and sustainable resource usage, improving nutrient utilization efficiency in dairy cows is an important task. Understanding the biology of feed efficiency in dairy cows enables for the development of markers that may be used to identify and choose the best animals for animal production. Thus in this study, ten Holstein cows were evaluated for feed efficiency and adipose tissue samples from five high efficient and five low efficient dairy cows were collected for protein extraction, digestion and data were analyzed for differential abundant proteins enriched in feed efficiency pathways. Among the identified peptides, we found 110 DAPs and two protein networks significantly related to feed efficiency. Among the relative mRNA expression of genes involved in energy metabolism including transcription/translation (STAT2, DDX39A and RBM39) or protein transport (ITGAV), only RBM39 showed significant decrease in high efficient dairy cows. The findings presented here confirmed the Transferrin upregulated in pathways including acute phase response signaling, LXR/RXR activation, FXR/RXR activation of high efficient dairy cows supporting that these pathways are related to feed efficiency in dairy cows.