Abstract: OBJECTIVE To explore the effect and the mechanism of clarithromycin on the transport of tacrolimus in Caco-2 cells. METHODS The concentration of tacrolimus was determined by chemiluminescence immunoassay. The single layer model of Caco-2 cells was established, the apparent permeability coefficient was calculated, and to compare the transport of tacrolimus in Caco-2 cell monolayer at different concentrations and the inhibition of tacrolimus transport by clarithromycin at different concentrations. RESULTS When tacrolimus concentration was 20, 40 and 80 μg·mL^-1, the absorption coefficient P_appAP-BL was (2.47±0.09)×10^-6, (3.91±0.17)×10^-6 and (4.49±0.16)×10^-6cm·s^-1, respectively, and the secretory coefficient P_appBL-AP was (6.05±0.21)×10^-6, (9.86±0.70)×10^-6and (11.75±0.28)×10^-6cm·s^-1 respectively; the apparent permeability ratio(PDR) was 2.45±0.03, 2.52±0.12 and 2.62±0.11 respectively. After adding different concentrations of clarithromycin(15, 30, 60 μg·mL^-1), the secretory permeability coefficient decreased significantly, but the absorption coefficient was not affected, and the PDR decreased significantly with the increase of clarithromycin concentration. CONCLUSION The extracellular transporters of Caco-2 may be involved in the transport of tacrolimus and the absorption tacrolimus could be apparently affected by combination of clarithromycin.