BACKGROUND & AIMS: It is unclear how the gut targeting medication mesalamine alters metabolic parameters associated with Metabolic Syndrome (MetS). We completed a retrospective analysis on ulcerative colitis (UC) and MetS comorbid patients receiving mesalamine to examine the effects of mesalamine on the metabolic risk factors associated with MetS. METHODS: We performed a retrospective chart review using Cerner Health Facts (from July 2007 to July 2017). We identified UC patients with a MetS comorbidity and who were prescribed mesalamine within +/- 7 days of an encounter in which they were diagnosed with UC. We then collected the patients blood pressure, labs, and body measurement index (BMI) for each of these patient at the index date and the closest values to 12 months after the index date. We used analysis of covariance (ANCOVA) to determine the effect of mesalamine therapy in patients with both UC and MetS on the metabolic parameters after 12 months of treatment compared to baseline. RESULTS: Our search of Cerner Health Facts identified 6,197 UC patients with concomitant MetS who were prescribed mesalamine. Of these individuals, 48% were female and 52% were male and within this cohort 88.3% received oral mesalamine and 11.7% received mesalamine via the rectal route. Oral mesalamine reduced fasting glucose levels and increased HDL cholesterol in these patients. C-reactive protein levels and erythrocyte sedimentation rate were also significantly reduced. Rectal mesalamine only reduced BMI. Further analysis revealed several MetS conditions risk factors were further improved when mesalamine was taken in the absence of medication for hypertension, hyperglycemia or dyslipidemia. CONCLUSION: In a retrospective chart study of UC-MetS patients, we found oral mesalamine improved several metabolic parameters associated with MetS. Our findings suggest the PPAR agonist mesalamine that targets the gastrointestinal tract could prove beneficial in improving hypertension, hyperglycemia and dyslipidemia.