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The toxicity of polybrominated diphenyl ethers (PBDEs), flame retardant components, was characterized in offspring from Wistar Han dams exposed by gavage to a PBDE mixture (DE71) starting at gestation day 6 (GD 6) and continuing to weaning on postnatal day 21 (PND 21). Offspring from the dams began PBDE direct dosing by gavage at the same dose as their dam on PND 12 – PND 21, and then after weaning, 5 days/week for another 13 weeks. Liver samples were collected at PND 22 and week 13 for liver gene expression analysis (Affymetrix Rat Genome 230 2.0 Array). PBDE treatment induced 1,066 liver gene transcript changes in females and 1,200 transcriptional changes in males at PND 22 (false discovery rate (FDR) < 0.01), but only 263 liver transcriptional changes at 13 weeks in male rats (FDR <0.05). No significant differences in dose response were found between male and female pups. Transcript changes at PND 22 coded for proteins in xenobiotic, sterol and lipid metabolism, and cell cycle regulation, and overlapped rodent liver transcript patterns after high fat diet or phenobarbital exposure. These findings, along with the observed PBDE-induced liver hypertrophy and vacuolization, suggests that long-term PBDE exposures have potential to modify cell functions that contribute to metabolic disease and/or cancer susceptibilities.