Objective To investigate the therapeutic effect of diosmetin on fetal faecal-induced acute lung injury in neonatal rats. Methods Fourty-eight neonatal male SD rats were enrolled. The rats were injected with 1.5 mL/kg fetal faecal by endotracheal intubation to replicate meconium lung injury model and randomly divided into 4 groups: control group, model group, methylprednil group and diosmetin group for subsequent experiments. Automatic blood gas analyzer was used to detect the arterial oxygenation index. Hematoxylin-eosin (HE) dye was used to detect the degree of lung tissue pathological injury and to evaluate the pathological score of lung injury. The lung tissue was removed and weighed 24 h after the establishment of lung injury model. The levels of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin- 6 (IL-6) were detected by enzyme-linked immunosorbent assay. The expressions of NOD-like receptor with pyrin domain 3 (NLRP3) inflammasome, cleaved caspase-1 (c-caspase-1) and IL-1β proteins were detected by Western blotting. Results Compared with the model group, the mean arterial oxygenation index of methylprednil group and diosmetin group decreased significantly (both P<0.05), and the pathological damage degree and lung injury pathological score were significantly reduced (both P<0.05), the levels of inflammatory factors TNF-α, IL-6 and IL-1β as well as the expressions of NLRP3, c-caspase-1 and IL-1β proteins were significantly lower (all P<0.01).Conclusion Diosmetin can down-regulate the levels of NLRP3, c-caspase-1 and IL-1β, as well as reduce the arterial oxygenation index and the levels of inflammatory cytokines, thereby can be used to treat neonatal rats with meconium-induced acute lung injury.