【Abstract】 Objective To establish rapid aging and cardiac aging mouse models through intraperitoneal injection of doxorubicin (DOX) at different doses and frequencies, optimize model evaluation indices, and provide disease model support for anti-aging drug evaluation. Methods (1) Rapid aging mouse model: mice were divided into model -1 group (5 mg/kg, once every 7 days), model -2 group (8 mg/kg, once every 10 days), model- 3 group (8 mg/kg, once every 7 days), model- 4 group (10 mg/kg, once every 10 days), and model -5 group (10 mg/kg, once every 7 days). Three intraperitoneal injections were administered, and mice were continuously observed for 60 days to record survival rate. (2) Cardiac aging mouse model: mice were divided into control group, model -1 group (2 mg/kg), model -2 group (5 mg/kg), model -3 group (8 mg/kg), and model- 4 group (10 mg/kg). Injections were given twice, once every 10 days, modeling lasted 30 days. After completion, small animal high-frequency ultrasound imaging technology (UBM) was used to evaluate ejection fraction (EF), fractional shortening (FS), and peak blood flow velocity; serum levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), interleukin 6 (IL-6), and interleukin 1β (IL-1β) were measured; myocardial tissue levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), succinate dehydrogenase (SDH), and catalase (CAT) were analyzed; myocardial tissue pathology, fibronectin (FN), β-galactosidase staining (β-gal), and p16 protein along with other cardiac aging-related indicators were assessed. Results: (1) Rapid aging mouse model: During the experiment, body weight and survival rate of mice in all modeling groups showed a significant downward trend. As DOX dose increased and modeling intervals shortened, decreases in body weight and survival rate became more pronounced. (2) Cardiac aging mouse model: Compared with the control group, DOX at 2, 5, 8, and 10 mg/kg significantly increased LDH levels (P < 0.01) and decreased GSH-Px activity (P < 0.05 or P < 0.01); DOX at 5, 8, and 10 mg/kg significantly decreased mouse body weight (P < 0.01), and EF, FS, as well as peak blood flow velocity were significantly reduced (P < 0.05 or P < 0.01). Serum IL-6 level increased significantly (P < 0.05 or P < 0.01), SOD content decreased significantly (P < 0.05 or P < 0.01), and β-galactosidase and p16 protein expression were significantly elevated (P < 0.05 or P < 0.01). Myocardial tissue showed hydropic and vacuolar degeneration; DOX at 8 and 10 mg/kg also significantly increased CK-MB levels (P < 0.01) and cardiac fibrosis (P < 0.01); additionally, DOX at 10 mg/kg increased IL-1β and MDA contents (P < 0.01). Conclusion: Intraperitoneal injection of DOX at 10 mg/kg once every 10 days for three injections successfully established a rapid aging mouse model; intraperitoneal injection of DOX at 5 or 8 mg/kg once every 10 days for two injections successfully established a cardiac aging mouse model, which induced changes in cardiac function, myocardial enzymes, inflammation, oxidative stress, aging markers, cardiac pathology, and fibrosis consistent with physiological and pathological characteristics of cardiac aging.