The roles of the pro-adipogenic ligands of the transcription factor Peroxisome Proliferator Activated Receptor gamma (PPARG) in regulating innate immune responses in bovine mammary epithelial cells (bMEC) were investigated using quantitative real-time PCR. The analyses revealed that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) enhanced the expression of Interleukin 8 (IL-8) and Chemokine (C-X-C motif) ligand 6 (CXCL6) in these cells in a dose-dependent manner. 15d-PGJ2 also induced the expression of transcripts encoding proteins involved in oxidative stress, including Ferritin heavy chain and Superoxide dismutase 1, as well as substantial microfilament reorganization. In contrast, synthetic PPARG agonists displayed a different and much smaller range of effects on the cells, causing down-regulation of Interleukin 1-beta, Interleukin 6 and IL-8 and increased expression of Chemokine (C-C motif) ligand 2 (CCL2) and Tumour necrosis factor alpha (TNFα). In an independent analysis, the cells were pre-incubated with PPARG agonists followed by lipopolysaccharide stimulation. This study revealed that troglitazone increased the responsiveness of the cells to lipopolysaccharide resulting in up-regulation of Interleukin 1-beta, TNFα, IL-8, CCL2 and CXCL6 while 15d-PGJ2 caused down-regulation of TNFα, CCL2 and CXCL6. These findings are relevant to understanding the anti-inflammatory potential of the PPARG ligands and underline different mechanisms of action of 15d-PGJ2 and troglitazone in bMEC. Furthermore, the present results demonstrate that the generation of pro-inflammatory mediators can be modulated by currently available therapeutic agents and may therefore be of value in the treatment of mastitis in ruminants.