<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>Total parental nutrition (TPN) causes gastrointestinal mucosal atrophy. The present study investigated the effects of hepatocyte growth factor (HGF) on the intestinal mucosal atrophy induced by TPN.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Rats underwent jugular vein catheterization and were divided into four groups: oral feeding (OF), TPN alone (TPN), TPN plus low-dose HGF (0.3 mg/kg/day; TPNLH), and TPN plus high-dose HGF (1.0 mg/kg/day; TPNHH). On day 7, rats were euthanized, and the small intestine was harvested and evaluated histologically. The expression of c-MET, a receptor of HGF, and nutrition transporter protein were evaluated using quantitative polymerase chain reaction.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The jejunal villus height (VH) and absorptive mucosal surface area in the TPNHH group were significantly higher than in the TPN group (<jats:italic>p</jats:italic> < 0.05). The VH in the ileum showed the same trend only in the TPNHH group, albeit without statistical significance. The crypt cell proliferation rate (CCPR) of the jejunum in both HGF-treated groups was significantly higher than in the TPN group (<jats:italic>p</jats:italic> < 0.01). The expression of c-MET and transporter protein in all TPN-treated groups was decreased compared with that in the OF group.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>HGF attenuated TPN-associated intestinal mucosal atrophy by increasing the villus height, which was associated with an increase in CCPR.</jats:p> </jats:sec>