Cucumis melo var. flexuosus (L.), snake melon or faqqous, is an ancient plant crop in many different parts of the world. The present study was designed to evaluate the efficacy of faqqous leaves extract on some blood respiratory functions in streptozotocin (STZ)-induced diabetic rats. Thirty five male albino rats were used in the current study and randomly divided into five groups: non-diabetic control group, diabetic control group (received a single intraperitoneal injection of 60 mg STZ/kg body weight), and other three diabetic groups treated orally with different doses of faqqous leaves extract (30, 60 or 120 mg/kg body weight) for 30 consecutive days. Induction of diabetes by STZ caused a significant decrease (P < 0.05) in most venous blood parameters including hemoglobin (Hb) content, hematocrit (Hct) value, oxygen partial pressure (PO2), percentage of O2 saturation (% O2), carbon dioxide partial pressure (PCO2), and the concentrations of bicarbonate (HCO3), total carbon dioxide (TCO2) and base excess (BE), as well as the logarithm of hydrogen ion (pH) of the arterial blood. Faqqous leaves extract (especially at 120 mg/kg body weight) modulated significantly almost all these changes in the blood of diabetic rats. Oxygen dissociation curve (ODC) shifted to the left in the diabetic control group compared with the non-diabetic control one; but shifted to the right in the diabetic groups treated with faqqous leaves extract. In conclusion, dietary supplementation of faqqous leaves extract improved significantly the blood respiratory functions of diabetic rats.