Although inflammation is a reactive to injurious stimuli and considered as beneficial process in body, but it causes some discomforts, such as pain. Murine dietary contains appreciable amounts of fatty acids and antioxidants which encourages researchers to focus on their potential therapeutic effects. This study is aimed to examine the analgesic and anti-inflammatory activity of Neptune krill oil (NKO) and fish oil (FO) in rodent model which are two well-known sources of rich content of n-3 polyunsaturated fatty acids (n-3 PUFAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). NKO and FO were used at the same dose of 500 mg and also balanced at similar doses of EPA: 12 in NKO vs. 12 in FO wt%, DHA: 7 NKO vs. 8 FO wt%. Application of NKO and FO in acetic acid-induced writhing effect, hot plate, and formalin induced test, indicated the nociceptive activity of the two tested drugs in comparison with normal saline. Also, the anti-inflammatory effect of these supplements was confirmed by carrageenan test. Analysis of cytokines levels in the blood samples of the mice after induction inflammation by carrageenan indicated decreased levels of those proteins compared to that in the normal groups. Both tested drugs, effectively could reduce severe inflammation and pain in rodents in comparison with the references drugs (depends on the tests); however, NKO was found to be more effective.