Purpose: Chronic nicotine administration induce various effects in whole organs of the body; however, little is known about salivary gland. In the present study, we pursued the links between systemic nicotine and the histomorphological changes of the salivary gland in mice. Methods: Twenty-five C57BL6 mice were allocated into two groups. The control group (n=9) received distilled water only for 8 weeks by gavage. The experimental nicotine group (n=16) was administered nicotine $5{mu}g/g$ with distilled water. Animals were sacrificed at 8 weeks; then, submandibular glands were excised and processed for histologic evaluation. Volumetric changes in acinar cells were evaluated by H&E staining. The expression of calponin-positive myoepithelial cells and Ki-67-positive proliferating acinar cells were evaluated by immunohistochemistry. Results: The nicotine group showed significantly decreased number of calponin-positive myoepithelial cell process compared with the control group. There were no significant differences in average volume of acinar cell and the number of Ki-67-positive acinar cells between both groups. Conclusions: These findings suggested that chronic nicotine administration may cause decreased function of myoepithelial cells in submandibular glands of mice, and these can partly explain xerostomic conditions in chronic smokers.