Background and Aim: Chelerythrine (CHE) is a quaternary benzo[c]phenanthridine alkaloid which has many potent pharmacological effects and can dissolve in water well,dihydrochelerythrine (DHCHE) has recently been identified as a CHE metabolite in rat.The aim of this study was therefore to find a suitable formulation to enhance the incorporation of CHE into LPs and improve therapeutic efficacy of CHE.Methods: The methods of preparation of liposomes (LPs) suffers from the drawback of poor incorporation of water-soluble drugs.Emulsion/solvent evaporation method is a relatively simple and efficient way to prepare LPs loaded with hydrophilic drugs.Results: The CHE-LPs has been successfully prepared by the emulsion/solvent evaporation method,the entrapment efficiency (EE%) of CHE was higher at 78.6% and the drug loadings (DL%) reached 7.8%.The relative bioavailability of CHE and its dihydro derivative in LPs were significantly increased compared with that of the CHE solution.The area under the plasma concentration–time curve (AUC) values of CHE and DHCHE after oral administration of CHE-LPs were 4.83-fold and 2.02 higher than those obtained with CHE solution.The half time (t1/2) and peak concentrations (Cmax) of CHE and DHCHE were also higher for CHE-LPs than that for CHE.In contrast,the total body clearance (CL),apparent volume of distribution (V/f(c)) were lower for CHE-LPs,in comparison to the respective parameter of CHE solution.Conclusion: It can thus be concluded that incorporation into LPs prolonged CHE retention within the systemic circulation.