Interestingly, in our study, the elimination of Trem2 or NFATc1 remarkably mitigated the beneficial effects of rhein applications in the ALI/ARDS model, suggesting that rhein mainly hindered the M1 polarization of macrophages and promoted the M2 polarization transition by interfering with the upstream signal (NFATc1) of Trem2 rather than the downstream signal (NF-κB), thus regulating the prognosis of ALI/ARDS. Here, TREM2 is linked to acute respiratory distress syndrome.