Docosahexaenoic acid (DHA), a representative ω-3 polyunsaturated fatty acid derived from fish oil, has been reported to have a wide spectrum of health beneficial effects. Timely resolution of inflammation at the early stage is important in preventing further progression to chronic inflammation and related disorders including cancer. Our recent studies have revealed that DHA enhances the efferocytic activity of macrophage, an essential event in resolution of inflammation. Moreover, DHA induced M2 macrophage polarization through peroxisome proliferator-activated receptor γ activation. Further, transgenic mice harbouring fat-1 gene capable of generating spontaneously n-3 polyunsaturated fatty acids including DHA were found to be less susceptible to experimentally induced murine colitis, skin inflammation, and photocarcinogenesis. DHA undergoes metabolism to produce biologically active electrophilic species. 17-Oxo DHA is one such reactive metabolite generated from DHA by cyclooxygenase-2 and dehydrogenase in activated macrophages. Our recent studies have demonstrated the amelioration of ultraviolet B (UVB)-induced oxidative stress, inflammation, and carcinogenesis in mouse skin as well as potentiation of efferocytic capability of murine macrophages by 17-oxo-DHA on. These effects were attributable to inactivation of proinflammatory transcription factors, such as NFkB and STAT3 and activation of the anti-inflammatory/proresolving transcription factor, NRF2. Therefore, DHA and its electrophilic metabolite 17-oxo-DHA may have a preventive potential in the management of human cancer which arises as a consequence of impaired resolution of inflammation as well as chronic inflammation.