Fenofibrate is a well known PPARa agonist and mediates its action as a hypolipidemic agent by regulating the expression of a variety of modulators of lipid metabolism, such as apoA-I, apoA-II and lipoprotein lipase. The mechanism underlying its anti-inflammatory effects, however are not clearly understood. It is known to interfere with NF-kB signaling by inducing expression of IkBa. In addition LTB4, the potent Methoxamine hydrochloride pro-inflammatory molecule that initiates, sustains and amplifies inflammation has been shown to be a ligand for PPARa. LTB4 through its action as PPARa agonist can enhance its metabolism, thus diminishing the inflammatory response. However, when the production of LTB4 is overwhelming then more potent agonist of PPARa may help enhance the metabolism of LTB4 thus reducing the inflammatory response. Recently, we demonstrated that the neuroprotective action of fenofibrate in a murine model of LPS mediated neuro-inflammation occurred through its ability to induce selective Pimozide Cyp4fs that effectively hydroxylated LTB4. However, prior administration of fenofibrate enhances the levels of 4f15 and 18, thus potentially increasing the metabolism of LTB4 to 20hydroxy LTB4 and a corresponding decrease in the levels of cytokines and chemokine. Interestingly we found that JEV infection per se decreases the levels of Cyp4f15 in a manner quite distinctive from the effects of LPS wherein 4f15 was induced. The mechanism underlying this distinctive effect of JEV infection is yet to be understood. Fenofibrate is known to inhibit the replication of Herpes simplex virus Type 1 and human immunodeficiency virus. The antiviral activity of fenofibrate is associated with the activation of PPARa receptors. Therefore, we examined the potential of fenofibrate to inhibit JEV replication and found a profound reduction in the viral titers both in vitro and in vivo when fenofibrate was administered 4 days prior to JEV challenge. To elucidate its mode of action, fenofibrate was also administered 2 days prior to JEV infection and found that it had no effect on the mortality, inflammatory response or viral replication quite unlike the dramatic protective effects seen when it was administered 4 days prior to JEV infection. Interestingly, this treatment paradigm also did not have any inducing effect on the Cyp4fs unlike the 4 days treatment with fenofibrate. Thus, the induction of Cyp4f15 observed after 4 days of fenofibrate pretreatment correlates with the neuroprotective effect seen, while shorter pretreatment which has no effect on Cyp4fs does not have any effect on the neurotoxicity seen after JEV infection. Therefore, it seems plausible that induction of critical genes including Cyp4fs through activation of PPARa is required for the anti-viral and anti-inflammatory effects seen following fenofibrate treatment. Nevertheless, the substantial anti-viral effect of fenofibrate demonstrated in this study is of significance and points to its potential therapeutic role in controlling JEV infection. One might question the usefulness of prophylaxis of drug if vaccination against JEV is possible. The inactivated mouse-brain derived, inactivated cell culture derived and live attenuated cellculture derived are the three types of JE vaccines used for immunization. However, their use is limited in terms of availability, cost and safety. In view of this, use of prophylatic drugs with good safety profile may be more effective in dealing with epidemic-like situation in endemic areas. In conclusion, we hereby demonstrate the effectiveness of fenofibrate administered prior to JEV infection to reduce mortality and prevent neurological dysfunction in survivors.