This study investigates the effects of mefepronic acid (MA), a PPAR-α agonist, on hepatic metabolic functions and reproduction of postpartum dairy cows. Sixty Friesian cows were divided into Group A (administered 5g of MA IM, within 24 hrs after calving, on the 3(rd) and 5(th) day postpartum) and Group B (control). All the cows were blood sampled within 24 hrs of calving (Day 0), on Day 3, 5, 10, 15, 30, and 40 postpartum. On plasma, metabolic and biochemical parameters were determined. Liver biopsies were performed on Day 0, 15 and 30 for the evaluation of hepatic lipid and glycogen content. Reproductive parameters were also evaluated. In Group A, blood HDL, glucose and cholesterol increased till the end of the study, in accordance with the histological results. PPAR-α immunopositive cells increased in liver slices of Group A, too. Reproductive parameters improved in Group A. This study highlights the beneficial effects of mefepronic acid on the hepatic metabolism and reproductive parameters of post-partum dairy cows.