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BACKGROUND The high mortality rate of lung cancer is highly associated with faster metastasis spread. All Trans Retinoic Acid (ATRA), being the first choice drug for leukemia therapy is now under intense study for its therapeutic efficiency in other solid cancers. OBJECTIVES This study was aimed to investigate the anti-metastasis activity of free ATRA and liposome entrapped ATRA (5:4:1) in the experimental C57BL/6 mice model developed by the injection of B16F10 cell line into the tail vein. METHOD The ATRA drug was given via i.p for 21 days. The visual lung and liver metastatic tumor nodules were noted. Various biochemical markers of cancer metastasis in the serum as well as tissues were also analyzed after sacrifice. RESULTS Tumor nodules have significantly decreased in ATRA treatment groups (32.83 ± 1.83 for free ATRA, 23 ± 2.36 for DSPC Lipo-ATRA) when compared with metastasis control (63.16 ± 2.9) in the lungs. Among the treatment groups, the DSPC lipo-ATRA treated group showed a significant tumor growth inhibition (63.6%) than that of in the free ATRA treated groups (48%). Similar anti-metastatic effect was observed in liver also. Furthermore lipo-ATRA has shown a significant change in the levels of biochemical cancer markers analyzed in this study. CONCLUSION Our results concluded that the liposome encapsulated ATRA has an enhanced anti-metastasis potency than the free ATRA during B16F10 metastatic cell line implantation.