AIM: To study whether etodolac enantiomers have pharmacokinetic difference after oral administration. METHODS:Fourteen rats, divided into two groups randomly, were orally given S-(+)- or R-(-)-etodolac at a single dose of 20 mg/kg, respectively. Blood samples were collected before and at 5, 10, 20, 30 min and 1, 3, 6, 12, 24, 48, 72 h after treatment. The plasma samples were analyzed with a high-performance liquid chromatographic method. RESULTS:The calibration curves were linear in the range of 0.5-50.0 mg/L (r=0.9999) to S-(+)-etodolac and 2.0-200.0 mg/L (r=0.9999) to R-(-)-etodolac, respectively. The main pharmacokinetic parameters of S-(+)- and R-(-)-etodolac were as follows: t1/2(λz) 18±4 h vs 19.4±2.2 h, tmax 3.3±2.6 h vs 4±4 h; Cmax 29±6 mg/L vs 97±14 mg/L, AUC0-t R-(-)-etodolac (P＞0.05). The Cmax, and AUC0-t of R-(-)-etodolac were markedly higher (P＜0.05), while the CL(s)and V/F were markedly lower than those of S-etolodac (P＜0.05). CONCLUSION: There is pharmacokinetic difference between S-(+)- and R-(-)- etodolac enantiomers in rats after oral administration.