This research paper addresses the hypothesis that dietary pioglitazone (PGT), as synthetic and specific ligand for PPAR-γ or walnut meal (WM) as a natural ligand for PPAR-γ, affect plasma metabolites and reduce the oxidative status in high body condition score (BCS) dairy cows (≥4 BCS). Total of 36 multiparous Holstein cows were randomly assigned to one of the dietary treatments: 1- Control (basal diet; CTR), 2- Walnut meal (9·45% walnut meal of DMI; WM), and 3- Pioglitazone (6 mg/kg BW; PGT). The experimental diets were fed from parturition time to 21 d postpartum. Results showed that the PGT supplementation increased dry matter intake (DMI) (22·95 kg/d) compared to the CTR (21·45 kg/d) and WM (21·78 kg/d) groups. Results showed that milk yield and milk composition were not affected by the experimental diets. Body condition score losses tended to be higher in the CTR group compared to the PGT and WM cows. The PGT group had higher plasma insulin compared to the CTR group (11·84 vs. 10·68 mIU/l), and WM cows had intermediate plasma insulin. The PGT cows had lower plasma non esterified fatty acid (NEFA) and tended to have lower β-hydroxy butyric acid (BHBA) than the CTR group. Feeding pioglitazone decreased plasma malondialdehyde (MDA) and increased plasma total antioxidant capacity (TAC) and superoxide dismutase (SOD) compared to the CTR and WM groups. It was concluded that dietary pioglitazone had positive effects on DMI, BCS change, blood metabolites and oxidative status in fresh dairy cows with high pre-calving BCS. The anti-oxidant effects of walnut meal were not supported by the present data.