Acute lung injury (ALI) is a life-threatening clinical problem with high mortality rate and limited treatments or preventive options that represents a major challenge for clinicians. Diacerein (DIA) is a multi-target anthraquinone derivative with potent anti-inflammatory action. The aim of this study is to assess the protective effect of DIA and its potential molecular targets against lipopolysaccharide (LPS)-induced ALI in rats.