Selaginella tamariscina is a traditional Chinese herb for the therapy of chronic trachitis and has been approved some anti-tumor activity. However, the anti-metastasis effects of Selaginella tamariscina in the lung cancer have not been understood clearly. The objectives of study were to investigate the effects of the Selaginella tamariscina extracts (STE) on the invasion and motility of highly metastatic A549 and Lewis lung carcinoma (LLC) cells. To further investigate the precise involvement of STE in tumor metastasis, A549 and LLC cells were treated with STE at various concentrations (0-100 microg/mL) for a specified period. The results from zymography showed that a STE treatment decreased (p<0.05) the expressions of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator (u-PA) in a dose-dependent manner in the A549 and LLC cell. Meanwhile, their endogenous inhibitors, which are tissue inhibitor of metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1), were increased in the A549 cell. Furthermore, the inhibitory effect of STE on the growth and metastasis of LLC cells in vivo was also proven. These results demonstrated that STE could be a candidate antimetastatic agent against lung cancer.