Abstract: OBJECTIVE To prepare sirolimus(SRL) polymer micelles and investigate its effects on the absorption kinetics of rat intestine. METHODS The SRL CS-DCA micelles were prepared by solvent evaporation using deoxycholic acid grafted chitosan(CS-DCA) as carrier. The encapsulation efficiency, drug loading, particle size and potential were taken as the evaluation indexes, and the formulation was optimized by the central composite design-response surface optimization method. In situ single pass perfusion model of rat was set up to investigate intestinal absorption characteristics of SRL CS-DCA micelles with different concentrations. Meanwhile, the intestinal absorption coefficient(P_eff), absorption rate constant(K_a) and the dose fraction(f_a) were used to evaluate drug absorption. RESULTS The optimum formulation of SRL CS-DCA micelles was as follows:the concentration of CS-DCA was 10 mg·mL^-1, and the mass ratio of drug to carrier was 20%. Under this condition, the system had the positive charge of (37.0±2.7)mV, particle size of (182.2±5.7)nm, the encapsulation efficiency greater than 90%, and the drug loading of (15.80±0.5)%. After the SRL CS-DCA micelles passed through the rat intestine, the P_eff, K_a and f_a were significantly higher than those of SRL(P<0.05). There was no significant difference in the P_eff, K_a and f_a values of SRL CS-DCA micelles with different concentration in the whole intestine of rats, suggesting that the micelles had no concentration inhibition at 10-100 μg·mL^-1, and the absorption characteristics were linear dynamics of passive transport. It was speculated that its possible absorption mechanism was passive diffusion. CONCLUSION The SRL CS-DCA micelles can enhance effect on intestine absorption of SRL monomer, which proves that SRL CS-DCA can effectively improve the oral bioavailability of sirolimus.