Abstract: Objective To observe the clinical effect of ulinastatin (UTI) combined with thymosin alpha 1 (Tαl) in the treatment of septic shock. Methods A retrospective analysis was conducted on the clinical data of 88 patients with septic shock admitted to our hospital from June 2021 to October 2023. The patients were divided into UTI group and UTI+Tα1 group according to different treatment methods, with 44 patients in each group. The treatment effects, clinical indicators, microcirculatory perfusion indicatorscentral venous oxygen saturation (S_cvO₂), lactate (LAC), capillary refill time (CRT), mean arterial pressure (MAP), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, immune indicators, plasma and serum inflammatory indicatorssoluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and prognosis were compared between the two groups. Results After 7 days of treatment, the effective rate of treatment in the UTI+Tα1 group was higher than that in the UTI group (P<0.05). The duration of vasoactive drug use, mechanical ventilation time, ICU stay, and hospital stay were shorter in the UTI+Tα1 group than those in the UTI group (P<0.05). After 24 and 72 hours of treatment, S_cvO₂ and MAP gradually increased, LAC gradually decreased, and CRT gradually shortened in both groups (P<0.05). After 24 hours of treatment, S_cvO₂ and MAP were higher, and CRT was shorter in the UTI+Tα1 group than those in the UTI group (P<0.05). After 72 hours of treatment, CRT was shorter, and MAP was higher in the UTI+Tα1 group than those in the UTI group (P<0.05). After 7 days of treatment, both APACHE Ⅱ and SOFA scores decreased in both groups compared to treatment before, and their scores were lower in the UTI+Tα1 group than those in the UTI group (P<0.05). After 7 days of treatment, the levels of CD3+ and CD4⁺ T lymphocytes increased in both groups compared to treatment before, and the levels were higher in the UTI+Tα1 group than those in the UTI group (P<0.05). After 7 days of treatment, the levels of sTREM-1, PCT, IL-6, and TNF-α decreased in both groups compared to treatment before, and the levels were lower in the UTI+Tα1 group than those in the UTI group (P<0.05). After a 28-day follow-up, there was no statistically significant difference in mortality between the two groups (P=0.398). Conclusion UTI combined with Tαl can effectively promote the recovery of patients with septic shock, improve microcirculatory perfusion, reduce plasma sTREM-1 and serum PCT levels, inhibit inflammatory responses, and improve prognosis.