Fibroblast growth factor 21 (FGF21) is a PPAR-α-regulated metabolic regulator that plays critical roles in glucose homoeostasis, lipid metabolism, insulin sensitivity and obesity. Conjugated linoleic acids (CLA), especially trans-10 (t-10), cis-12 (c-12), have shown anti-obesity properties. In addition, CLA is reported as a high-affinity ligand and activator of PPAR-α. This raises the possibility that FGF21 might be involved in the anti-obesity effect of CLA. In the present study, we tested the hypothesis that FGF21 expression in the liver could be induced by t-10, c-12-CLA through PPAR-α. HepG2 cells were treated with 100 μm-bovine serum albumin, 10 μm-t-10, c-12-CLA or 100 μm-t-10, c-12-CLA for 8 h. A total of ten adult C57BL/6J mice were fed with the diets containing 1 % soya oil or t-10, c-12-CLA for 5 d. t-10, c-12-CLA stimulated hepatic FGF21 mRNA abundance as determined by real-time RT-PCR. t-10, c-12-CLA also increased serum FGF21 concentrations as measured by an ELISA. Co-transfection analysis indicated that reporter gene expression from the mouse FGF21 promoter was induced by t-10, c-12-CLA in a PPAR-α-dependent manner. Taken together, these results suggest that t-10, c-12-CLA induces hepatic FGF21 expression through PPAR-α. This FGF21 and PPAR-α linkage may provide another potential explanation for the anti-obesity effect of t-10, c-12-CLA.