Object: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors induce body weight loss through urinary glucose excretion. However, the observed body weight loss was less than expected. Compensatory hyperphasia seemed to be one of the mechanisms. Butyrate is a short chain fatty acid which is produced by gut microbiota fermentation, and might have beneficial effects on appetite regulation and metabolic improvement. In this study, we investigated the effect of combination treatment of dapagliflozin and butyrate on fat reduction in db/db mice. Methods: Six-week-old male db/db mice were assigned into four groups: vehicle with chow diet (CD), dapagliflozin with CD, vehicle with 5% sodium butyrate-supplemented CD (SB), or dapagliflozin with 5% SB. Dapagliflozin (1mg/kg) was administered via oral gavage for six weeks. Body weight, random blood glucose, and food intake were measured daily. Baseline and follow-up body composition was measured by DEXA. After 6-week treatment insulin sensitivity was evaluated by insulin tolerance test. Results: The increase in body weight was attenuated in vehicle with SB and dapagliflozin with SB groups than vehicle with CD group. These two groups showed decreased food intake. The dapagliflozin with SB group showed the lowest value in the change of total and abdominal fat tissue from baseline. Blood glucose was decreased and insulin sensitivity was increased in three treatment groups compared to vehicle with CD group. Hepatic steatosis and brown adipose tissue morphology tended to be improved especially in the combination group. Conclusion: Butyrate supplement decreased whole body and abdominal fat gain, and tended to have beneficial effects on fatty liver in db/db mouse when treated with dapagliflozin.