BACKGROUND: The aim of our work was to investigate the effects of omega-3 polyunsaturated fatty acids on apoptosis and granzyme B, perforin, and cation-independent mannose 6-phosphate/insulin-like growth factor receptor (CI-MPR) expression of intestinal epithelial cells of chronic rejection after small intestinal transplantation. METHODS: Small bowel transplantation was performed in a rat combination of 3 groups: group 1, Lewis-to-Lewis; group 2, F344-to-Lewis, dietary corn oil; group 3, F344-to-Lewis, dietary fish oil. All recipients were killed at 16 weeks posttransplantation. The apoptosis rate of mucosal cells was evaluated by flow cytometry. The expression of granzyme B, perforin, and CI-MPR was analyzed by reverse transcriptase PCR. RESULTS: A high apoptotic rate was observed when the allografts demonstrated 1 or more histologic features of chronic rejection. omega-3 Polyunsaturated fatty acids decreased in rate of the apoptosis, and it can inhibit the expression of granzyme B, perforin, and CI-MPR. CONCLUSIONS: omega-3 Polyunsaturated fatty acids can suppress the rejection to mucosal cells of allograft at the time of chronic rejection in small intestinal transplantation, which may be significant in increasing the surviving rate of allograft, delaying the chronic dysfunction, and prolonging the lifetime of both allograft and acceptor.