The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally Escherichia coli-induced mastitis. At time = 0, each of 16 periparturient dairy cows received 20-40 colony-forming units of live E. coli in one front quarter of the udder. A time series of liver biopsies was collected at -144, 12, 24, and 192 h relative to time of inoculation. Changes in transcription levels in response to E. coli inoculation were analyzed using the Bovine Genome Array and tested significant for 408 transcripts over the time series [adjusted p ≤ 0.05, abs(fold-change) > 2]. After 2-D clustering, transcripts represented three distinct transcription profiles: 1) regulation of gene transcription and apoptosis, 2) responses to cellular stress invoked by reactive metabolites, and 3) metabolism and turnover of proteins. The results showed that the liver went through a period of perturbations to its normal homeostatic condition during the first 24 h following the E. coli-induced intra-mammary inflammation. In previous studies, bacterial lipopolysaccharide, LPS, was used for intramammary stimulation to mimic E. coli infection. Comparing responses to LPS and E. coli, induced biochemical processes were similar but not identical (94 and 85% similarity between corresponding samples at early and late acute phase, respectively), but their kinetics were not. A notable difference concerned transcription of factors associated with oxidative stress in E. coli-induced liver responses.