Polyunsaturated fatty acids (PUFA) have therapeutic effects in inflammatory diseases, however the specific mechanisms by which they exert these effects have not yet been defined. Several studies have shown involvement of toll llke receptor TLR2 and TLR4 in some of these inflammatory diseases shown to be inhibited by PUFA, In order to detemine how PUFA exert their beneficial effects in these diseases it is important to examlne how PUFA modulate the expression and actlvatlon of TLR2 and TLR4 and the downstream signalling pathways This study investigates the effects of a number of PUFA, including conjugated lrnoleic acld (CLA), docosahexaenolc acid @HA) and eicosapentaenolc acld (EPA), on MAP hnase signaling pathways and cytolune production in macrophages following achvation of these cells through these TLRs Macrophages are key cells involved in activation of innate immune responses. Ths study used the J774 munne macrophage cell line as a model. The results demonstrate that PUFA exert distinct effects on both pro-inflammatory and anti-inflammatory cytokine production depending on whether the cell is achvated via TLR2 or TLR4 Thus, providing evidence that the effects of PUFA on immune cell function are highly dependent on the mode of activation of the cell. Furthermore, individual PUFA exert these effects through differentral regulation of MAP kinase signalling protelns Activation of ElCK was found to be critical for mediating the effects of PUFA on cytokine production, with p38 being involved to a lesser extent. Given that these fatty acids can change the way in which an immune cell responds to activation through TLRs, further research must be undertaken in order to fully elucidate the benefits of dietary supplementation with fatty acids and indeed to determne any drawbacks associated with their use