The effects of protocatechuic acid (PCA) on hepatic activity and/or mRNA expression of lipogenic enzymes and sterol regulatory element-binding proteins (SREBPs) in mice fed a trans fatty acid (TFA)-rich diet were examined. PCA at 1, 2, or 4% was provided for 10 weeks. Results showed that TFA diet significantly enhanced hepatic activity and mRNA expression of fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, stearoyl-CoA desaturase-1, and SREBP-1c (P<0.05); however, the intake of PCA significantly diminished the activity and mRNA expression of these lipogenic factors and decreased hepatic lipid accumulation (P<0.05). TFA diet significantly increased hepatic levels of TFA and pro-inflammatory cytokines (P<0.05). However, PCA intake significantly lowered hepatic content of 18:1 trans and 18:2 trans, as well as reduced the level of test cytokines (P<0.05). These results indicate that PCA is a potent agent for attenuating TFA-induced hepatic steatosis.