The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC((0-t)), AUC((0-∞)), and C(max) for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t(1/2β)) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC((0-t)), AUC((0-∞)), and C(max) for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t(1/2β)) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t(1/2β), and C(max) of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD).