Objectives Multidrug resistance 1 (MDR1) encodes a protein called P-glycoprotein (P-gp), which serves as an efflux pump membrane protein implicated in intestinal homeostasis and drug resistance. Cyclooxygenase-2 (COX2) is a key enzyme in the synthesis of proinflammatory prostaglandins, tumourigenesis and in mucosal defence. Despite the importance of MDR1 and COX2, changes in their mRNA levels have not been studied in cats with inflammatory bowel disease (IBD) and low-grade alimentary lymphoma (LGAL). The present study aimed to determine the mRNA levels of MDR1 and COX2 in cats with IBD and LGAL, and to evaluate their correlation with clinical signs, histological severity and between genes. Methods Cats diagnosed with IBD (n = 20) and LGAL (n = 9) between 2008 and 2015 were included in the current study. Three healthy animals composed the healthy control cats group in which endoscopy was performed immediately before the ovariohysterectomy. All duodenal biopsy samples were obtained by endoscopy. Feline chronic enteropathy activity index was calculated for all cases. IBD histopathology was classified according to severity. MDR1 and COX2 mRNA levels were determined by absolute reverse transcriptase-quantitative real-time PCR. Results Statistically significant differences were observed for MDR1 and COX2 mRNA levels between the IBD and LGAL groups. No correlations were observed between molecular gene expression, feline chronic enteropathy activity index and histological grading for IBD, and between MDR1 and COX2 genes. However, a positive statistically significant correlation was observed between MDR1 and COX2 expression in the duodenum of cats. Conclusions and relevance MDR1 and COX2 gene expression is increased in cats with LGAL compared with cats with IBD. The control group tended to have lower values than both diseased groups. These results suggest that these genes may be involved in the pathogenesis of IBD or LGAL in cats.