2,4-Thiazolidinedione (TZD), a peroxisome proliferator-activated receptors agonist, modulates metabolism and inflammation. The objective of this study was to determine the effect of TZD on lipid soluble vitamins in goats with sub-clinical mastitis. The study included 2 experiments. In exp. I: 24 Saanen lactating dairy goats receiving low-energy diet without vitamins supplement. Six goats in each group received a daily IV injection of either 8 mg/kg BW of TZD or saline. A week later, goats were challenged with intramammary infusion (IMI) of saline (CTZD or CTRL) or Streptococcus uberis (MTZD or MCTR). Blood samples were obtained on d −7, −2, 1, 2 and 12 relative to IMI. In experiment II, 12 Saanen lactating dairy goats received supplemental lipid-soluble vitamins. Six goats in each group were injected with 8 mg/kg BW of TZD or saline daily, followed by an IMI of Streptococcus uberis 14 d later. Blood samples were obtained on d −15, 0, 1, 10 and 11 relative to IMI. Serum samples were analyzed for retinol, α-tocopherol, β-carotene, 13-cis retinoic acid and all-trans retinoic acid. Data were analyzed using the Proc Mixed of SAS with significance declared at P ≤ 0.05. In experiment I, MTZD on d 1, 2 and 12, showed lower retinol concentration compared with CTRL. On d 2, MTZD had a lower retinol concentration compared with MCTR. However, β-carotene in MTZD group was greater compared with CTRL and MCTR on d 12. No significant difference was observed among treatments in experiment II. In conclusion, during sub-clinic mastitis with low energy diets and inadequate vitamins, treatment with TZD may mobilize retinol toward inflammation. Treatment with TZD did not seem effective when goats were supplemented with lipid-soluble vitamins.