HSG4112, a racemic drug, is a new anti-obesity agent. In this study, the stereoselective pharmacokinetics of HSG4112 were investigated in rats and dogs, and the underlying mechanism was investigated. The plasma concentrations of HSG4112(S) and HSG4112(R) were quantitated in plasma from rats and beagle dogs after IV and/or oral administration of racemic HSG4112. The concentration of HSG4112(S) was significantly higher than that of HSG4112(R) in rat plasma. Contrarily, the concentration of HSG4112(R) was significantly higher than HSG4112(S) in dog plasma. A metabolic stability test with liver microsomes showed that HSG4112(S) was more stable than HSG4112(R) in rat liver microsomes, but the difference between stereoisomers did not appear in dog liver microsomes. However, the stereoselectivity was observed in dog liver and intestinal microsomes after uridine 5’-diphospho-glucuronic acid was added. Thus, stereoselective metabolism by uridine 5’-diphospho-glucuronosyltransferases is mainly responsible for the stereoselective pharmacokinetics in dogs. These results suggest that the species difference in the stereoselective plasma pharmacokinetics of HSG4112 is due to the stereoselective metabolism.