Human health is severely threatened by sepsis due to its high incidence, disability, and mortality rates. Animal models serve as a critical experimental foundation for investigating the molecular pathogenesis of sepsis, facilitating early diagnosis, and developing precision treatment strategies. Among these, the cecal ligation and puncture (CLP) model remains the most widely used in sepsis research. Its reproducibility and reliability depend on strict control over multiple factors, including surgical details, perioperative care, rat strain, age and sex, seasonal and circadian rhythms, and pharmacological variables. Based on a comprehensive analysis of 83 studies published between December 1, 2023, and December 1, 2024, this review analyzes the critical determinants of model severity, sources of systematic heterogeneity, and pharmacological variables. Our analysis aims to clarify the control elements of CLP model construction, improve modeling success rates, enhance research reproducibility and external validity, and ultimately increase the clinical translational value of model-derived data.