Abstract: Maternal smoking has been clearly demonstrated to be associated with increased health problems in infants and children. Nicotine is the chemical substance with high level of toxicity. It crosses through the placenta and accumulates in the developing organs of fetus. Previous investigation indicated that maternal nicotine exposures induce decreased fibronectin expression in lung parenchyma. In this study, the effect of maternal nicotine exposure on laminin expression of the newborn mice lungs has been evaluated. Female pregnant Balb/C mice were divided randomly in to four groups as fallow: Experimental group1 (Exp D1); was received 3 mg kg-1 nicotine intra peritoneal injection (IP) from gestational day 7 (GD7) to the last day of pregnancy, Experimental group 2 (Exp D14); was received 3 mg kg-1 nicotine from GD7 to postnatal day 14, Groups 3 and 4; as sham control groups (Sha-Con) were received the same volume (3 mg kg-1) of normal saline parallel to experimental groups. At the end of exposure times, all of newborns were anesthetized; their lungs were removed and prepared for immunohistochemical method and real-time polymerase chain reaction. The finding indicated that laminin alpha 5 (Lama5) mRNA expressions in the lung of newborn in the nicotine treated Exp D1 decreased by 0.63 fold but increased in Exp D14 by 1.57 fold comparing to Sh-Con groups. Lama5 immunoreactivity was not similar in different parts of the lungs including alveoli and bronchiole, having a significant increase in the experimental groups in contrast to the Sh-Con groups. However, increase in immunoreactivity observed more in Exp D14. Immunoreactivity intensity in small vessels of all experimental groups was not significantly different. These data also indicate that maternal nicotine exposure may induce abnormal laminin expression which may cause defects in lung function during life time.