Abstract: AimTo investigate the preparation of diclofenac sodium pulsatile release pellets (DS-PRP), the release In Vitro and the pharmacokinetics of the drug. MethodsDiclofenac sodium (DS) core pellets prepared by extrusion-spheronization technology were coated in a mini-fluidized bed spray coater with swelling material as the inner coating swelling layer and ethylcellulose aqueous dispersion as the outer coating controlled layer. The effects of formulation and medium on pulsatile release of DS were investigated under release rate test. Pharmacokinetic and bioavailability study in eight human subjects were performed by HPLC method. Results The delayed-release time and release rate of DS from DS-PRP were influenced obviously by the swelling material, the concentration of SDS in medium, the coating level of the inner swelling layer and the outer controlled layer. In vitro, the delayed-release time t_0.1 was 3.1 h, and the pulsed-release time t0.1-0.8 was 1.2 h. In vivo, the delayed-release time tlag was 2.8 h, and the bioavailability was （91±12）%. Conclusion The release of drug from DS-PRP was shown to be in pulsed way both In Vitro and in vivo.