Malignant melanoma is an aggressive cancer of neuroectodermal origin. The mechanisms of n-3 polyunsaturated fatty acids (PUFAs) against melanoma metastasis are not clear. Here fat-1 and wild type (WT) mice were injected with B16F10 melanoma cells via the tail vein to establish lung metastasis model. Endogenous n-3 PUFAs were associated with a reduction in grossly visible pulmonary metastases and outgrowth through inhibition of mesenchymal to epithelial transition (MET), which was characterized by decreased expression of epithelial markers E-cadherin and ZO-1, and increased expression of mesenchymal marker vimentin in tumour tissues from fat-1 mice compared with WT controls. In addition, n-3 PUFA-mediated inhibition of MET may have been associated, in part, with the: (i) formation of n-3 PUFA-derived lipid mediators and (ii) decreased expression of mature IL-1β and p-NF-κB, and enhanced expression of superoxide dismutase-1. These results suggest that n-3 PUFAs exert their antitumourigenic activities, in part, via their anti-inflammatory properties.