Among causes of acute pancreatitis, hypertriglyceridemia has gained increasing recognition, with a higher prevalence in Asian populations. Intravenous insulin infusion is the primary treatment for hypertriglyceridemia-induced acute pancreatitis (HTGP). However, the effectiveness and safety of insulin therapy may vary depending on baseline triglyceride levels and individual insulin resistance. Additionally, the necessity of rapid triglyceride reduction to prevent disease progression remains unclear. This study aims to assess the efficacy and safety of insulin infusion in HTGP patients with varying triglyceride levels and evaluate its impact on disease progression. This prospective study enrolled 54 patients aged 18 years or older diagnosed with HTGP and treated with insulin infusion between October 2022 and June 2023. Diagnosis and severity classification followed the 2012 revised Atlanta criteria. Patients received continuous intravenous insulin following a standardized protocol. Patients were stratified into 2 groups based on median baseline triglyceride levels: high (<25.455 mmol/L) and extremely high (≥25.455 mmol/L). Triglyceride levels were measured at baseline and at 12, 24, 48, and 72 hours posttreatment, along with other biochemical and clinical parameters. Differences in mean change from baseline and other indices between the 2 groups were compared and the association between triglyceride reduction and disease progression was assessed. Statistical significance was set at P < .05. A total of 54 patients (mean age: 48 ± 10 years, 88.9% male) were included in the study. Baseline characteristics, including age, body mass index, and history of diabetes, pancreatitis, gallstones, and alcohol consumption, were similar between the high and extremely high triglyceride groups (all P > .05). Triglyceride levels decreased significantly in both groups, with a greater reduction observed in the extremely high group at all time points. A greater triglyceride reduction within the first 12 hours was significantly associated with a lower risk of worsening pancreatitis (odds ratio 0.642, 95% confidence interval 0.347–0.892, P = .049). Continuous intravenous insulin infusion is a safe and effective treatment for reducing triglyceride levels in HTGP. Early triglyceride reduction, particularly within the first 24 hours, plays a crucial role in preventing disease deterioration.