We investigated the effects of alpha lipoic acid (ALA) on blood and lung tissue exposed chronically to cigarette smoke (CS). Female Sprague-Dawley rats were divided into three groups. Group 1 was the control group (CON): fresh air was supplied twice daily and 0.1ml physiological saline was given orally for 8weeks. Group 2 was exposed to CS: 12 cigarettes were smoked daily at two sessions for 1h and 0.1ml saline was given orally for 8weeks. Group 3 (CS + ALA) was exposed to 12 cigarettes daily in two sessions for 1h and 100mg/kg/day ALA was given orally for 8weeks. DNA damage was assessed using comet analysis; oxidative damage was assessed using ischemia-modified albumin (IMA) from blood; and total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured in blood and lung tissue. Histopathological and immunohistochemical evaluation of hypoxia-inducible factor (HIF)-1, and -2, caspase-3, vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF(2)) were conducted using lung tissue. The oxidative markers, TOS, OSI and IMA, and the comet analysis score were increased and the TAS level was decreased in the blood of the CS group compared to the CON group. IMA levels in blood, and TOS and OSI levels in the lung were decreased significantly in the CS + ALA group compared to the CS group. We observed increased septal wall thickness, marked and diffuse inflammatory reaction, emphysema, and necrotic cell debris in bronchial and bronchiolar lumens in the CS group. HIF-1, HIF-2, caspase-3 and FGF(2) expressions were increased, while VEGF expression decreased in the lung tissues of the CS group compared to the CON group. ALA slightly ameliorated the damage caused by chronic exposure to CS in the lungs, but further investigation is needed to determine its possible protective effects at different dosages.