Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, - plays anti-inflammatory role in atherosclerosis, and has surfactant-releasing effects in lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin-4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin-4 and STZ. Exendin-4 (3 μg/kg) was administered daily by subcutaneous injection for 30 days after mice were rendered diabetic with a single dose of STZ (200 mg/kg). Structural alterations, oxidative stress, apoptosis, insulin signaling and expressions of prosurfactant-C, alpha-smooth muscle actin, collagen-I and fibronectin were evaluated in lung tissue. Diabetic mice lungs were characterized by induced oxidative stress, apoptosis, edema, and cell proliferation. They had honeycomb-like alveoli, thicker alveolar walls, and hypertrophic pneumocytes. Although exendin-4 treatment improved pulmonary edema, apoptosis, oxidative stress, and lung injury, it led to the disrupted insulin signaling and interstitial collagen accumulation in the lungs of diabetic mice. Exendin-4 ameliorates hyperglycemia-mediated lung damage by reducing glucose, -oxidative stress and stimulating cell proliferation. However, exendin-4 led to increased lung injury partly by reducing insulin signaling - and collagen accumulation around pulmonary vasculature in diabetic mice.