Introduction: Antiangiogenesis agents have promise in initiating cancer implantation and growth. Troponin I is an antiangiogenic compound derived from cartilage. Its functional segment resides at amino-acid 96-116. We studied the effects of this peptide (pTnI) on a) endothelial cell tube (capillary progenitor) formation, b) endothelial cell division, c) induction of intercellular adhesion molecule-1 (ICAM-1) by pancreatic cancer cells (CAPAN-1) and d) growth of pancreatic cancer liver metastases in the mouse. Methods: a) Human vascular endothelial cells (HUVEC) were seeded on a basement membrane matrix, incubated with graded concentrations of pTnI, and tube formation was evaluated histologically. b) HUVEC were labeled with carboxyfluorescein diacetate succinimidyl ester (CFDA,SE), incubated +/- pTnI, and fluorescence measured at 96 hours by flow cytometry to determine cell division. c) ICAM-1 expression was measured by flow cytometry on HUVEC incubated with CAPAN-1 and treated +/- pTnI. d) CAPAN-1 cells were injected into the spleen of nude mice pre-treated with 3.5 mg/kg/day of pTnI, and body weight, liver weight and tumor burden were measured at 6 weeks. Results: a) pTnI inhibited endothelial cell tube formation (p<0.0001) at concentrations as low as 1pg/ml. b) Endothelial cell division was inhibited significantly at 96 hours by 3mg/ml pTnI (p=0.0001). c) Supernatant from CAPAN-1 cells upregulated ICAM-1 on HUVEC by 96%. This upregulation was diminished by pre-incubation of CAPAN-1 cells with less than 10ng/ml pTnI (p<0.01). d) Mice treated with pTnI had fewer liver metastases compared to controls (liver/body weight 5.5% versus 11.1%, p<0.05). Conclusion: The peptide 94-123 of Troponin I has an antiangiogenic effect in pancreatic cancer. In-vitro it inhibits pre-vessel tube formation, endothelial cell division, and ICAM-1 upregulation by cancer cells, and in-vivo it reduces metastases from pancreatic cancer to the liver in a mouse model.