The effects of a fish-meal-and potato-protein-based diet enriched with omega-3 PUFA on intestinal inflammatory activity and expression of genes active in fatty acid (FA) uptake were tested in the duodenum of dogs with food responsive diarrhea (FRD; n ¼ 14) and inflammatory bowel disease (IBD; n ¼ 7). The clinical outcome was estimated by monitoring the canine IBD activity index (CIBDAI) before and after treatment. Dogs were treated with the diet alone (FRD) or the diet in combination with immunosuppressants (IBD). The duodenal mRNA levels of FA translocase, FA transport protein-1,-3,-4,-6, long chain acyl coenzyme synthetase-1,-4,-5,-6, liver-and intestinal-FA binding proteins, interleukin-1b (IL)-1b and -6, and tumor necrosis factor-a were measured by quantitative PCR. The CIBDAI significantly decreased after treatment in all dogs. The mRNA levels of target genes were associated both with disease phenotype and dietary treatment. Significantly different expression patterns were found for IL-1b, FA translocase, intestinal-FA binding protein, FA transport proteins-1,-3,-6, and long chain acyl coenzyme synthetase-5,-6. In conclusion, the mRNA levels of some of the genes involved in duodenal FA uptake may be altered by a fish-meal-and potato-protein-based diet enriched with omega-3 PUFA. This may be beneficial for the treatment of canine chronic enteropathies, particularly FRD.Practical applications: In this study, feeding dogs on a fish-meal-and potato-protein-based diet enriched with omega-3 PUFA resulted in marked suppression of intestinal inflammatory activity, mainly in the duodenum of dogs with food responsive diarrhea with a concomitant alteration of some of the genes involved in FA uptake. In IBD, however, a combination of diet and immunosuppressive drugs was required. The present study provides preliminary insights into the importance of the herein tested dietary composition for the treatment of canine chronic enteropathies, revealing that an omega-3 PUFA-enriched diet can be beneficial to the animal's health and wellbeing. Furthermore, our results serve as the basis for future investigations using different food ingredients and FA compositions to identify the optimal dietary mixture that could be equally effective for dietary prophylactic or therapeutic treatment of canine chronic enteropathies, or both.Keywords: Canine inflammatory bowel disease index activity / Fatty acid transporters / Intestinal bowel disease / Omega-6 and omega-3 fatty acids