Background <p>Farnesoid X receptor (FXR) is known to play important roles in glucose and lipid metabolism. We aimed to evaluate effects of FXR agonist on metabolic disorders in <i>db/db</i> mice. Seven week-old <i>db/db</i> mice were injected FXR agonist GW4064 (30&#xa0;mg/kg/day) or carrier solution (dimethyl sulfoxide) intraperitoneally for 4&#xa0;weeks. Body weight, food intake, and blood glucose levels were measured weekly. Glucose tolerance test and insulin tolerance test were performed at the end of study. Hepatic genes involed in lipogenesis and gluconeogenesis were analyzed by real time polymerase chain reaction. Endoplasmic reticulum stress markers were analyzed by western blot.</p> Results <p>GW4064 treatment significantly attenuated weight gain, and improved glucose intolerance and insulin resistance in <i>db/db</i> mice. In addition, GW4064 treatment significantly repressed hepatic steatosis. GW4064 treatment significantly lowered hepatic gene expression of <i>phosphoenolpyruvate carboxykinase 1</i>, <i>glucose 6-phosphatase</i>, and <i>sterol regulatory element binding protein 1c</i>. GW4064 treatment significantly lowered the protein levels of ATF6, CHOP, Caspase3, and Cleaved Caspase3 in liver. FXR agonist GW4064 showed beneficial effects on weight gain, glucose intolerance, insulin resistance, hepatic steatosis, and hepatic ER stress.</p> Conclusions <p>These findings suggest that FXR agonists are promising therapeutic agents for treatment of various metabolic disorders.</p>