Basic research on estrogen related changes in cardiomyocyte gene expression is needed to provide a greater understanding of the effects of estrogen, so that hormone replacement trials and treatment can be based on a true comprehension of estrogen’s pleiotropic effects. Therefore, we compared gene expression in models of estrogen depletion and estrogen replacement. Using gene expression array analysis, we examined differences in expression in cardiac tissue from ovariectomized (OVX), ovariectomized with 17-estradiol replacement (OVX/E2), and intact rats undergoing sham procedures (Sham). We found that OVX results in at least two-fold changes in expression of genes involved in inflammation, vascular tone, apoptosis, and proteolysis, compared to OVX/E2. With confirmation via real time PCR, we found an OVX induced increase in genes mediating inflammation (inhibin a, IL-6, TNF-, SOCS2, SOCS3), an OVX related decrease in the myocardial mRNA expression of genes involved in regulating vasodilation (eNOS, soluble guanyl cyclase), an OVX associated increase in extracellular matrix genes (collagen121, connexin 43), and an OVX related increase in pro-apoptotic genes (caspase 3, calpain). Because details of cardiac signaling by SOCS genes are virtually unknown, we examined the protein expression for these genes via western analyses. Although we observed OVX related increases in SOCS2 and SOCS3 mRNA, SOCS2 and SOCS3 protein did not differ among groups. In light of these findings, investigation into the net effect of OVX on inflammation is warranted. These experiments add to existing evidence that estrogen can protect against negative changes associated with estrogen removal.