PURPOSE: This study was designed to investigate the benefits of intravenous (IV) and luminal administration of Hepatocyte Growth Factor (HGF) on a rat model of inflammatory bowel disease (IBD). METHODS: Transfection of the HLA-B27 gene into Fischer rats induces a phenotype similar to IBD. Fischer rats and HLA-B27 rats were divided into six groups: Fischer rats, IV saline (n=6); HLA-B27 rats, IV saline (n=6); HLA-B27 rats, IV HGF (150 µg/kg/day; n=6); Fischer rats, luminal saline (n=5); HLA-B27 rats, luminal saline (n=5); and HLA-B27 rats, luminal HGF (150 µg/kg/day; n=6). HGF or saline was infused for 14 days via an osmotic pump attached to a catheter inserted into either the internal jugular vein or the terminal ileum. Following treatment, rats were evaluated for diarrhea on a scale from 1 (normal stool) to 4 (severe diarrhea with mucous). Gross analysis of bowel lesions was scored by two blinded reviewers. Microscopic analysis of the ileum, cecum, and colon was assessed by a blinded pathologist and each section was scored on a scale of 0 (normal) to 3 (severe inflammation). A microscopic inflammation score was determined by adding the three individual scores together. Statistics were determined using ANOVA. A pvalue of < 0.05 was significant. RESULTS: See Table. IV administration of HGF decreased diarrhea in the treatment group by 41% (p<0.05). Gross analysis of IV HGF-treated animals revealed a 31% decrease in total bowel lesions compared to untreated HLA-B27 rats, but did not achieve statistical significance. Microscopic inflammation was reduced 54% in IV HGF treated rats (p<0.05). Luminal HGF exposure produced a 53% decrease in total bowel lesions and a 75% decrease in small bowel lesions (p<0.05). Luminal HGF treatment also reduced microscopic inflammation by 40% compared to untreated HLA-B27 rats (p<0.05), but it had no effect on diarrhea. CONCLUSIONS: HGF administration, either IV or luminally, ameliorates many signs and symptoms of IBD in this unique immunologic rat model of IBD. HGF administration is a promising new therapy in the management of IBD.