Objective To study the role of the phosphoinositide 3-kinase (PI3K) / Akt/ mammalian target of rapamycin (mTOR) signaling pathway in the pathogenesis of transfusion-related acute lung injury (TRALI) in rats. Methods A rat model of TRALI was established via trauma-blood loss-massive transfusion, and pulmonary histopathological changes were detected by hematoxylin and eosin staining. Protein and mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in peripheral blood or lung tissues were detected by enzymelinked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction, respectively. Expression levels of PI3K/ Akt/ mTOR signaling pathway-related proteins and of the apoptosis-related proteins Bax, Bcl-2, and Caspase3 were detected by Western blot. Results Alveolar tissue structure was seriously damaged and inflammatory cell infiltration and edema were evident in TRALI model rats. Expression levels of the inflammatory cytokines TNF-α, IL-6, and IL-1β were significantly increased in peripheral blood and lung tissues (P<0. 05). The PI3K/ Akt/ mTOR signaling pathway was activated, the p-mTOR/ mTOR ratio was significantly increased, expression levels of the apoptotic proteins Bax and Caspase3 were inhibited, and expression of the anti-apoptotic protein Bcl-2 was increased (P<0. 05). Conclusions mTOR, as a potential drug target, may represent an important strategy for the clinical prevention and control of TRALI, by defining the exact timings of its protective and damaging effects and selecting the optimal medication time, in light of the complex mechanism of TRALI.