Abstract: Cyclosporine A-loaded human serum albumin nanoparicles(CyA-HSA)were prepared and physicochemical properties including entrapment efficiency, drug-loading capability, particles size, Zeta potential, morphology, pH value and osmotic pressure were evaluated. Dialysis was undertaken to investigate the release of CyA from CyA-HSA nanoparticles in vitro. The obtained CyA-HSA nanoparticles showed spherical shape with mean particle sizes of 240. 5 nm and Zeta potential of -32. 0 mV. The drug-loading amount and entrapment efficiency were 14. 7% and 85. 8%, respectively. The pH and osmotic pressure of nanoparticles were 7. 0 and 314. 7 mOsmol/kg, respectively. CyA-HSA nanoparticles exhibited better dilution stability than commercial cyclosporine A injection, Sandimmune^® . Both CyA-HSA and Sandimmune^® exhibited significant sustained release behavior in vitro and both release profiles displayed a zero-order process. The pharmacokinetic study at equal administration dosage(7 mg/kg)in rats showed that cyclosporine A concentration-time data were in accordance with the two-compartment model. The CL and k₁₀ of CyA-HSA significantly decreased and AUC significantly increased compared to those of Sandimmune^® (P< 0. 05). CyA-HSA nanoparticles showed obvious solubility enhancement, sustained release and less side effect and toxicity resulting from solubilizing agent of Sandimmune^® , Cremophor EL, and might be developed as the next generation dosage form of cyclosporine A.