Acute lung injury (ALI) describes the injury to endothelial cells in the lungs and associated vessels due to various factors. Furthermore, ALI accompanied by inflammation and thrombosis has been reported as a common complication of SARS-COV-2 infection. It is widely accepted that inflammation and the cytokine storm are main causes of ALI. Two classical anti-inflammatory cell types, regulatory T cells (Tregs) and M2 macrophages, are theoretically capable of resisting uncontrolled inflammation. Recent studies have indicated possible crosstalk between Tregs and macrophages involving their mutual activation. In this review, we discuss the current findings related to ALI pathogenesis and the role of Tregs and macrophages. In particular, we review the molecular mechanisms underlying the crosstalk between Tregs and macrophages in ALI pathogenesis. Understanding the role of Tregs and macrophages will provide the potential targets for treating ALI.