Abstract: The aims of this study were (1) to investigate the effect of maternal nicotine exposure, during gestation and lactation, on the lung histological structures of rat offspring and its reversibility and (2) to establish whether carnosine would protect the neonatal rat lung against the adverse effects of maternal nicotine exposure. After mating, the pregnant albino rats were divided into three groups; group I (control group) received a daily subcutaneous injection of normal saline, group II received a daily a subcutaneous injection of nicotine (1 mg kg-1 body weight) and group III received daily both of subcutaneous injection of nicotine (1 mg kg-1 body weight) and intramuscular injection of carnosine (10 mg kg-1 body weight). The lung tissue of the rat pups was collected for histological and histomorphometric study on postnatal days 7, 21 and 49. The study showed that maternal nicotine exposure resulted in marked affection of the lung parenchyma of the rat pups including massive cellular infiltration, thickening of the alveolar septa with increase of their cellularity, proliferation and migration of Type II pneumocytes, damage of the elastic tissue and increased fibroblast deposition. Loss of normal lung architecture and rupture septa with coalescence of alveoli giving picture of microscopical emphysema were also noticed. There was also significant decrease in the alveolar count mm-2 and the percentage of elastic tissue fibers with significant increase in the percentage of collagen fibers in the lung parenchyma of these rat pups, compared with age-matched controls. These changes were irreversible as they progressed even after withdrawal of nicotine following weaning, implying that these changes could be induced at gene level. The treatment with carnosine limited the deleterious effects of nicotine on the histological structure of lung parenchyma of rat pups especially the alveolar count, which did not show significant changes compared with the age-matched controls, as time laps. However, carnosine did not prevent completely the induction of microscopic emphysema resulted from maternal nicotine exposure.