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Hypertrophic cardiomyopathy up‐regulates HIF‐1α and PPARγ to cooperatively to mediate important changes in cardiac metabolism that are characteristic of and contribute to common forms of heart disease. HIF‐1α activates glycolytic genes, and PPARγ facilitates the uptake of free fatty acids uptake and genes involved with glycerol‐lipid biosynthesis in response to pathologic stress. Therefore, these changes increase the rate of glycolysis and glucose‐to‐lipid ratio via glycerol‐3‐phosphate pathway, apoptosis, and contractile dysfunction. However, the expression of genes regulated by HIF‐1α and PPARγ in physiologic hypertrophy induced by pregnancy and its reversible process (postpartum) are not well defined. In the present study, we quantified HIF‐1α (HK2, PFKM, GAPDH and PK4) and PPARγ (GPAT and GPD1) target genes before (not pregnancy, NP), during late pregnancy (LP, 21 days) and after pregnancy (PP, 7 days) in the left ventricle of rats. Levels of mRNA for the glycolytic genes HK2, PFKM and GAPDH increased 1.6‐, 3.2‐ and 2‐ fold during LP and decreased to basal level after PP, respectively, while PK mRNA levels decreased during LP and returned to basal level after PP. The glycerol‐lipid biosynthesis genes GPAT and GPD1 increased 14‐ and 3‐ folds during EP and decreased to basal levels after PP, respectively. Results demonstrate that pregnancy induces the expression of glycolytic and glycerol‐lipid biosynthesis genes suggesting a shift in cardiac metabolism by activation of HIF‐1α and PPARγ.