Abstract: AimTo develop a less toxic alternative for sandimmun neoral (Neoral). To study the preparation conditions and to compare its pharmacokinetic characteristics with Neoral. MethodsPolylactide nanoparticles loaded cyclosporine A was prepared by solvent-nonsolvent method. Polylactide nanoparticles were administered by oral in a dosage of 15 mg·kg^-1. The CyA concentration in whole blood sample was determined by HPLC. ResultsThe quantities of CyA, PLA and volume of acetone added had significant influence on the NP diameters. Under proper condition, the nanoparticles with diameters of 57.5 nm were obtained. The relative bioavailability in rats was 101.6%, with a smaller absorption rate (P<0.05) and a smaller elimination rate (P<0.1). ConclusionThe nanoparticles (diamater<100 nm) with relative high bioavailability were prepared using solvent-nonsolvent method. It is suitable for further study.