Objective By studying the effects of different modeling cycles on related indicators in a hydroxyureainduced kidney-yang deficiency animal model, the optimal modeling time was obtained. The stability of the model was evaluated. We provide method for creating a stable animal model of warming and tonifying kidney-yang to treat yangdeficiency syndrome. Methods Rats were gavaged with 30 mg/ mL hydroxyurea suspension (300 mg/ kg body weight) once daily for 28 days. On the 7^th, 14^th, 21^st, and 28^th days of gavage, the general condition, biochemical indexes related to kidney-yang deficiency, and the morphology of the internal organs were examined to determine the optimal modeling cycle. Results On the 7^th day of hydroxyurea gavage, the energy metabolism of rats with kidney-yang deficiency induced by hydroxyurea was assessed, and their body temperature, activity of kidney Na⁺ -K⁺ -ATPase, serum content of cAMP, and cAMP/ cGMP ratio were significantly decreased ( P< 0. 05). There were no significant changes in the rats’ neuroendocrine systems, immune functions, or urogenital systems. On the 14^th day of hydroxyurea administration, serum cGMP increased significantly (P< 0. 05) and total ATPase activity decreased significantly (P< 0. 05). There were no significant changes in the temperature of the extremities or tails of the rats or kidney Ca²⁺ -Mg²⁺ -ATPase activity (P> 0. 05). Levels of the neuroendocrine system indicators serum T and T4 were significantly decreased (P< 0. 05). In the urogenital system, there were structural pathological changes to the kidney and testis, and the kidney index decreased significantly (P> 0. 05). On the 21^st day of hydroxyurea gavage, the temperature of the extremities and tails of rats and the kidney activity of Ca²⁺ -Mg²⁺ -ATPase were significantly decreased (P< 0. 05). The neuroendocrine system indicators urine 17-OH-CS and serum T3 levels were significantly decreased (P< 0. 05). On the 28^th day of hydroxyurea gavage, the immune function indicator, the spleen index, decreased significantly (P< 0. 05), and thymus pathological changes were significant and irreversible. In the urogenital system, pathological changes to the kidney and testis were significant and irreversible. Energy metabolism, neuroendocrine system, immune function, and urogenital system indexes still showed decreasing trends on day 28, but there were no significant differences in energy metabolism, neuroendocrine system, or urogenital system indicators compared with on day 21 (P> 0. 05). Conclusions We found significant differences among the modeling time periods for each energy metabolism, neuroendocrine, immune, and urogenital function index, and other aspects, of a hydroxyurea-induced rat model of kidney-yang deficiency. The best modeling time was 28 days.