Oxygen from the pulmonary capillaries is transported by the blood flow to the tissues. At the tissue level, O₂ leaves the tissues' capillaries and reaches the interior of the body cells. CO₂ produced by the body cells follows the same way in reverse.

The lungs have two circulations: 1) the bronchial, supplying oxygenated blood from the systemic circulation to the tracheobronchial tree, and 2) the pulmonary, bringing the mixed venous blood from the right heart to the alveolar capillaries, and oxygenated blood back to the left heart. The term "mixed" venous blood is used to indicate that blood comes from different body organs with different metabolic activities (different O₂ consumption and CO₂ production).
 

The blood is spread out in a multitude of thin-walled vessels which have a surface area estimated at 100 m² or 40 times the body surface area. The pulmonary circulation differs in many ways from the systemic one. Blood pressure in the pulmonary circulation is lower than in the systemic circulation. The walls of the pulmonary capillaries are thinner than those of similar vessels in the systemic circulation. Normally the right ventricle develops a pressure of about 25 mmHg during its systole, and this is transmitted to the pulmonary arteries. When systole ends, right ventricle pressure falls to atmospheric (0). Since the pulmonary valves are now closed blood pressure in pulmonary circulation decreases gradually during diastole to a low of about 8 mmHg as blood flows through the pulmonary capillaries. The mean pulmonary artery pressure is about 14 mmHg. Left arterial pressure is about 5 mmHg.

Blood flow depends on vascular pressure. Total pressure drop from pulmonary artery to left atrium is about 10 mmHg while in the systemic circulation it is about 100 mmHg. Therefore, the pulmonary vascular resistance is only one tenth of that of the systemic circulation. The low vascular resistance in the pulmonary circulation relies on remarkably thin vascular walls. The low vascular resistance and high compliance of the pulmonary circulation allows the lung to accept the whole of the cardiac output at all times. On the other hand, because of their high compliance, the pulmonary vessels are liable to collapse. Distension and closure of these vessels depend on the pressure within and around them. When the pressure around them (alveolar pressure) increases above the pressure inside the capillaries, they collapse. Therefore, at large lung volumes and increased alveolar pressure, the pulmonary capillaries collapse. Changes in lung volume affect large vessels differently. Both the arteries and the veins increase their caliber as the lung expands. They are pulled open by the radial traction of the surrounding lung parenchyma. Moreover, these vessels are exposed to intrapleural pressure (see chapter on lung mechanics).

The pulmonary circulation has the capacity to accommodate twofold to threefold increases in cardiac output with little change in the pulmonary artery pressure (as during exercise). The increase in blood flow with little changes in driving pressure indicates that as pulmonary blood flow increases, pulmonary vascular resistance falls. This fall in vascular resistance results from an increasing cross-sectional area of the vascular bed. Blood vessels already perfused may increase their caliber (distension). Also vessels previously closed may open as the cardiac output rises (recruitment).

Drugs (serotonin, histamine, norepinephrine) which cause the contraction of smooth muscle increase pulmonary vascular resistance in the larger pulmonary arteries. Drugs (acetylcholine, isoproteranol) which can relax smooth muscle decrease pulmonary vascular resistance.

Pulmonary blood flow is affected by gravity and it differs with body posture. In the upright position, blood flow increases almost linearly from the top to the bottom of the lungs (Fig. 10).