ScopeIt has been suggested that n‐3 PUFA can be used as a preventive or therapeutic strategy to control allergic asthma. But little is known about the exact mechanisms by which n‐3 PUFA modulates it. Here, the effects of elevated n‐3 PUFA on ovalbumin (OVA) induced airway inflammation were investigated using Fat‐1 transgenic mice that can convert n‐6 PUFA to n‐3 PUFA endogenously.Methods and resultsFirst, we tested whether Fat‐1 expression modulates CD4+ T‐cell activation, proliferation, and differentiation in vitro and found that the Fat‐1 expression attenuated all of these CD4+ T‐cell responses by suppression of T‐cell receptor mediated signaling and cytokine‐mediated phosphorylation of STATs. When the Fat‐1 mice were sensitized and challenged with the OVA, they showed a significant decrease in the recruitment of inflammatory cells into airway, the production of Th2 cytokines, eotaxin, and mucin in the lung, and the concentration of OVA‐specific IgE in the serum. Furthermore, the differentiation of CD4+ T cells into Th2 was also decreased in the spleen of Fat‐1 mice.ConclusionOur results showed that an elevated level of n‐3 PUFA was effective in preventing allergic airway inflammation by modulating the activation and differentiation of CD4+ T cells in Fat‐1 mice.