The present study revealed that PPARα signaling activated by fenofibrate could improve mitochondrial β-FAO and recover the disorder of bile acid metabolism, and decrease the oxidative stress and inflammation cytokines in alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis, suggesting the potential use of PPARα agonists as therapeutic alternatives for cholestatic liver damage. The gene discussed is PPARA; the disease is cholestasis.