Acute lung injury (ALI) is a severe form of diffuse lung disease, which imposes a substantial health burden all over the world. The immune system plays a key role in the development of ALI. The aim of the study was to investigate the expression of cytotoxic T-lymphocyte antigen 4 (CTLA4) in ALI. Levels of CTLA4 were tested on CD4+ and CD8+ T cells in 62 ALI cases and 75 healthy controls by flow cytometry. Data revealed that prevalence of CTLA4 on CD4+ T cells was significantly increased in ALI patients (3.7%±2.1%) than in controls (0.7%±0.3%). Similarly, the proportion of CTLA4 on CD8+ T cells was also significantly elevated in cases (1.0%±0.4% versus 0.5%±0.1%, p<0.05). Further analysis showed that the frequency of CTLA4+CD4+ T cells was positively correlated with the score of Acute Physiology and Chronic Health Evaluation II (APACHE II) (p=0.0005). In addition, when investigating CTLA4 expression with ALI patient mortality, we observed that the level of CTLA4+CD4+ T cells in patients was higher at the time before death than at the time of recruitment (p=0.001). These data suggested that CTLA4 was involved in the pathogenesis and progression of ALI and could be used as a potential target for treating this disease.