As one member of the nuclear receptor family, the human pregnane X receptor (hPXR) is found to activate cytochrome P450-3A expression in response to a wide variety of xenobiotics and play a key role in mediating adverse drug-drug interactions. Three crystal structures of hPXR have been successively solved by Watkins et al. during recent years, including one apo structure and two complexing with SR12813 and Hyperforin respectively. Also quite a few EC50 values for PXR activation derived from hPXR ligands have been obtained by competition binding assays. To disclose how PXR interacts with structure-diverse ligands, we use molecule docking programs Dock4.0, FlexX and Autodock3 to dock about 40 activators of hPXR into the receptor. Docking results show that nearly all these activators can be docked into the ligand binding pocket of hPXR, except for one relatively large molecule, Rifampicin,which may bind to PXR in another different way.