Aims: Feeding pregnant rats a low protein diet has been shown to have deleterious effects on placental development and induce an altered phenotype in the adult offspring. The aim of this study was to investigate the effects of maternal dietary restriction on the expression of the whole placental transcriptome in order to identify molecular processes involved. Methods: Rats were fed one of three diets: control (C, 18% casein), protein restricted (PR, 9% casein) or 30% reduction in total food intake (UN) from conception. On day 18 of gestation dams were culled and the placentas collected. The placental transcriptome (6 pooled placentas per dietary group) was analysed by Oxford Gene Technology (OGT, Oxford, UK) using an Agilent 14879 whole rat genome expression microarray (4 X 44K) G4131F (Agilent Technologies Inc., USA). Altered gene networks were identified using gene ontology analysis (GeneSifterTM; www.genesifter.net; VizX Labs LLC, Seattle, USA). Molecular pathways identified by the microarray analysis were investigated further using quantitative real-time PCR to measure transcript levels for specific genes (6 placentas per dietary group). Data were normalised using the endogenous control gene cyclophilin and analysed by one-way analysis of variance with Bonferroni’s post hoc test. Results: 4264 genes differed (>1.5-fold change) between placentas of PR and C dams (1631 increased, 2633 decreased). 4575 genes differed between placentas of UN and C dams (2004 increased, 2571 decreased). Gene ontology analysis showed that maternal PR and UN induced changes (Z score >2) in the gene ontology pathways: detection of stimulus, signal transducer activity and lipid metabolic processes were increased, while developmental processes and ion transport were decreased. PCR revealed that fatty acid transport protein (slc27a5), lipoprotein lipase and thioredoxin-interacting protein mRNA levels were increased in UN compared to C and PR placentas (P<0.05), whereas peroxisome proliferator-activated receptor (PPAR) alpha mRNA levels were increased in UN compared to PR placentas (P<0.05). PPAR delta mRNA levels were unchanged. Conclusions: This study demonstrates that an altered maternal diet can affect the expression of the placental transcriptome with some similarities between dietary exposures. Lipid metabolism and PPAR signalling were identified as key pathways in the placental response to altered total maternal nutrition. The effects are specific to the dietary challenge which suggests that the placenta may act as a nutrient sensor. By making specific changes in gene expression in response to a particular maternal diet the placenta may alter its function in order to adapt fetal development to suit that environment.