Abstract: Objective To investigate the preventive effects of thymosin-α1 against early ventilator-associated pneumonia (VAP) in the patients with mechanical ventilation. Methods Fifty two patients with expectancy of mechanical ventilation over 48 h were divided into routine therapy group (n=26) and thymosin therapy group (n=26) in random. The patients in routine therapy group were given intensive care unit (ICU) conventional treatment, and the patients in thymosin therapy group were given thymosin treatment additionally (1.6 mg subcutaneous injection, qd×7 d). The incidence and occurrence time of VAP were observed, and the time of mechanical ventilation and ICU stay were recorded. The levels of CD3⁺,CD4⁺,CD4⁺/CD8⁺T lymphocyte, CD14⁺ mononuclear cell human leukocyte antigens-DR (CD14⁺ HLA-DR) and procalcitonin (PCT) were detected before mechanical ventilation and at the 3^rd and 7^th d after mechanical ventilation. Results The base line including the level of immunologic function had no difference between the two groups ( P>0.05). The incidence of VAP in thymosin therapy group was lower than that in routine therapy group，but it was not significant difference ( P>0.05). The durations of machine ventilation and ICU stay in thymosin therapy group were shorter than those in routine therapy group ( P<0.05). The occurrence time of VAP in thymosin therapy group was significantly later than that in routine therapy group （ P<0.05）. At the 3^rd and 7^th d after mechanical ventilation, thymosin therapy group achived higher levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺T lymphocyte and CD14⁺ HLA-DR than routine therapy group did （ P<0.05）. Conclusion Thymosin-α1 may be able to improve immunologic function and prevent the incidence of early VAP in the patients with mechanical ventilation.