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Background: The purpose of the present study was to evaluate the effects of ω-3 fatty acids (Omegaven) on early intestinal adaptation in rats with short bowel syndrome (SBS)., Methods: Male Sprague-Dawley rats were randomly assigned to 1 of 4 groups: sham rats underwent bowel transection; SBS rats underwent 75% bowel resection; SBS-O ω-3 rats underwent bowel resection and were treated with oral Omegaven given by gavage; and SBS-I ω-3 rats underwent bowel resection and were treated with Omegaven given intraperitoneally. Rats were killed on day 14. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depths, cell proliferation and apoptosis) were determined at time of death. Real-time polymerase chain reaction was used to determine the level of Bax and Bcl-2 messenger RNA (mRNA). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test, with P < .05 considered statistically significant., Results: Oral ω-3 supplementation did not significantly change intestinal regrowth. In contrast, parenteral ω-3 in rats that underwent resection resulted in higher bowel and mucosal weights, mucosal DNA and protein in ileum, villus height in ileum, crypt depth in jejunum and ileum, and greater rates of cell proliferation in jejunum and ileum compared with SBS animals. The initial decreased levels of apoptosis corresponded with the early decrease in Bax and increase in Bcl-2 mRNA levels., Conclusions: Parenteral but not enteral Omegaven augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased apoptosis reflect increased cell turnover in Omegaven-treated animals.