While many studies have examined the pregnancy and health-related outcomes of delayed motherhood for women, less is known concerning the potential consequences for their children. This study aims to investigate the effect of delayed motherhood on the hippocampus at the whole genome level. Sprague-Dawley rat females, either at the age of 3 or 12 months, were individually housed with a randomly selected 3-month-old male. The rat whole genome expression chips were used to detect gene expression differences in the hippocampus of newborn rats. The gene expression profile was studied through gene ontology and signal pathway analyses. qRT-PCR was used to determine the mRNA expression of solute carrier family 2 (SLC2A1) and S-phase kinase-associated protein 2 (SKP2). Western blot was used to detect the protein expression of SKP2. Compared to the control group, 1291 differentially expressed genes were detected, including 635 up-regulated genes and 656 down-regulated genes. These differential expressed genes were involved in 110 significant biological process and nine significant signaling pathways, in which the pathway in cancer is the most changed pathway. For SKP2 (up-regulated) and SLC2A1 (up-regulated) genes which were relevant to the pathway in cancer, qRT-PCR results were consistent with gene chip assay results. The upregulation of SKP2 was also demonstrated at protein level. In conclusion, delayed motherhood led to unique patterns of hippocampal gene expression in offspring and the newly identified genes afford a quantitative view of the changes which enable deeper insights into the molecular basis underlying the role of delayed motherhood.