Cigarette smoking is known to induce serious lung diseases, but there is not an effective method to solve this problem. The present study investigated vitamin D3 on over-expression of CXCR3 and CXCL10 in mice induced by cigarette smoking. A pulmonary airway model was designed, and morphological assessment of emphysema, IL-4, IFN-γ and CXCL10 concentration in bronchoalveolar lavage fluids, expression of CXCR3 and CXCL10 were detected. Emphysema of the mice only exposed to cigarette smoke was significant, and concentration of IL-4, IFN-γ and CXCL10 was also increased. In addition, CXCR3 and CXCL10 were over-expressed. The degree of emphysema, concentration of IL-4, IFN-γ and CXCL10, and expression of CXCR3 and CXCL10 in mice administrated with low dose vitamin D3 were similar to the normally treated mice. Low dose of vitamin D3 can effectively protect the lung from the damage induced by cigarette smoke.