The effect of conjugated linoleic acid (CLA) on pre-existent peritoneal metastasis was examined by mouse peritoneal metastasis models. The cell growth of LL2 mouse cancer cells was suppressed by CLA in a dose-dependent manner. CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma. C57B6 mice were inoculated with LL2 cells into their peritoneal cavity. Two weeks after inoculation, colonized peritoneal cancer foci (2.2+/-0.4 mm in diameter) were treated with CLA administrated intraperitoneally (200 or 600 pmol/mouse, twice a week). CLA treatment decreased the number of peritoneal tumors: 8.7+/-0.6, 5.7+/-0.6, and 2.3+/-0.6 in untreated, 200 pmol/mouse CLA, and 600 pmol/mouse CLA groups, respectively (P<0.0001). CLA treatment decreased the size of peritoneal tumors: 3.7+/-1.5, 1.3+/-0.5, and 1.0+/-0.4 mm in untreated, 200 pmol/mouse CLA, and 600 pmol/mouse CLA groups, respectively (P<0.0001). In CLA-treated tumors, proliferating cells were decreased (P<0.0001), whereas apoptotic cells were increased (P=0.0010). CLA-treated LL2 tumors showed decrease of PPARgamma and EGFR proteins and increase of BAX protein in comparison with untreated tumors. These findings suggest that CLA possesses anti-tumor capability to peritoneal metastasis.