We evaluated global placental gene expression in intrauterine growth restriction (IUGR; n = 8) compared to normal pregnancies (n = 8) and studied possible additional effect of preeclampsia. Placental samples were collected from IUGR pregnancies due to placental insufficiency ascertained by hemodynamic studies. Four IUGR pregnancies were associated with preeclampsia. Gene expression profile was evaluated by 30k oligonucleotide microarrays. Principal component analysis (PCA) showed good separation in terms of gene expression patterns between the groups. Pathway analysis showed upregulation of inflammation mediated by chemokine and cytokine signaling pathway in the IUGR placentas. Genes involved in placental glucocorticoid metabolism were also differentially expressed. None of the known imprinted placental genes were differentially expressed. Subgroup analysis between IUGR placentas with and without preeclampsia showed few (n = 27) differentially expressed genes. In conclusion, IUGR due to placental insufficiency appears to alter placental glucocorticoid metabolism, upregulates inflammatory response in placenta, and shares common pathogenic mechanisms with severe early-onset preeclampsia.