Interleukin-12 (IL-12) is known to exert anti-tumor immune effects by promoting the activation and proliferation of T cells and NK cells within the immune system. However, clinical trials have observed systemic toxicity associated with the administration of IL-12. This has shelved development plans for its use as a cancer therapeutic drug. Therefore, it is critical that we perform a systematic evaluation of the toxicity and safety of repeated IL-12 administration. In this study, we conducted a comprehensive evaluation of the toxicity and safety of repeated IL-12 administration in rhesus monkeys by assessing its effects on the immune system, organ function, and vital signs. Our findings provide accurate dosage selection and administration plans that minimize the risk of adverse reactions in patients while ensuring therapeutic efficacy.