Introduction: Apoptosis is a type of cell death that is essential for homeostasis. Findings on the impact of physical activity on apoptosis are contradictory. The aim of this study was to investigate the effect of high intensity interval training with curcumin on gene expression of Bax, Bcl- 2, and Caspase- 3 in aged female rat hepatocytes. Methods: In this experimental study, 35 aged female, postmenopausal Wistar rats (2-year-old), were randomly assigned to five groups including control, curcumin, high intensity interval training (HIIT), curcumin with HIIT and sham. Curcumin was given at 30 mg/kg by gavage in experimental groups 3 days a week. The HIIT protocol consisted of three sessions of high intensity treadmill training per week for 8 weeks. Forty-eight hours after the last training session and gavage, the Bax, Bcl- 2, and Caspase-3 genes expression were measured in the hepatocytes. Results: The expression of Bax (P = 0.0003) and Caspase- 3 (P = 0.0006) genes increased significantly due to HIIT, while curcumin reduced this increase (P≤0.05). Bcl- 2 gene decreased due to HIIT (P = 0.001), and Curcumin with HIIT increased Bcl- 2 (P≤0.05). Conclusion: HIIT and curcumin had an antagonistic effect on expression of apoptosis-regulating genes in hepatocytes