Diabetes mellitus (DM) is a dysmetabolic disease characterized by chronic hyperglycemia. In the developed countries, DM is the commonest life style disease that afects both old and young age. Nod-like receptor protein-3 (NLRP3)-mediated pyroptosis may in fact aid in the development of diabetic complications. Quercetin is a natural favonoid, can be present in natural foods and plants. Many studies have reported the antioxidant role of quercetin on diferent tissues, but its efects on NLRP3-mediated pyroptosis in diabetic lung are unclear. The current study aimed to assess quercetin’s protective efects on lung function, oxidative stress, and NLRP3-mediated pyroptosis in Wister rats exposed to streptozotocin (STZ)-induced DM. Forty male Wister rats were randomly allocated into four equal groups. The groups of rats were as follows: group 1 (G1) was kept under normal control conditions; G2 was injected I/P quercetin at a dose of 30 mg/kg b.wt., daily for 30 days; G3 and G4 were injected with a single dose of streptozotocin (STZ) 50 mg/kg b.wt. I/P to induce DM. After 72-h post diabetes induction, the rats of G4 were treated with quercetin as a manner in the second group. The results showed that quercetin ameliorates the pulmonary dysfunctions caused by DM through restoring the levels of glucose, insulin, and arterial blood gases, as well as the oxidative markers. Also, NLRP3-pyroptosis-mediated IL1β was inhibited. Quercetin also reduces the efect of DM on the lung by decreasing the pathological changes in the lung. In conclusion, NLRP3 infammasome-induced pyroptosis may aggravate lung injury in diabetic rats. Quercetin has the potential to ameliorate diabetes induced pulmonary dysfunction by targeting NLRP3.