Objective To investigate the protective effect and mechanism of cyclic peptide OCP 2 on myocardial tissue of high-altitude hypoxic mice. Method 60 male Balb/c mice were randomly divided into 6 groups: normal control group, hypoxia model group, acetazolamide group, and OCP 2 low-, medium-, high- dose groups. After a single intraperitoneal administration of the corresponding medication for 10 minutes, each group was placed in a simulated altitude environment of 8000 meters. Heart tissue was collected 24 hours later to observe pathological changes in myocardial tissue, measure levels of oxidative stress and inflammatory factors, measure levels of HIF-1α, Nrf2, PGC1α, PPARγ. Compared with normal control group, the myocardial tissue cells in the hypoxia model group were disordered and swollen, with lighter staining and significantly higher pathological scores (P<0.01); SOD, CAT, and GSH were significantly decreased (P<0.01), while MDA, TNF-α, IL-1 β, IL-6, HIF-1α, and Nrf2 expression levels were significantly increased (P<0.01). The expression levels of PGC-1α and PPARγ were significantly reduced (P<0.01). Compared with the hypoxia model group, the pathological scores of cardiac tissue in each dose group of OCP 2 were significantly reduced (P<0.01), and the degree of muscle fiber swelling and misalignment was alleviated; The contents of SOD, CAT, and GSH, as well as the expression levels of PGC-1 α and PPAR γ were significantly increased (P<0.01), while the contents of TNF-α, IL-1β, IL-6, MDA, and the expression levels of HIF-1α and Nrf2 were significantly decreased (P<0.05 or P<0.01). Conclusion: OCP 2 has a good protective effect on myocardial tissue damage in high-altitude hypoxic mice, which may be related to the effective inhibition of HIF-1α activity, thereby disrupting its synergistic effect with Nrf2 and PPAR γ/PGC-1 α signaling axes, ultimately inhibiting the production of inflammatory factors and improving antioxidant capacity