It is a challenging and important project to prolong the in vivo half life of protein and peptide drugs by physicochemical methods without new molecular entities generation.  Protein crystallization provides a new strategy for improving the stability and in vivo delivery of these drugs.  We show here that recombinant human interferon-alpha (rhIFN) can form spherical crystals.  The physical and chemical features of the crystals were characterized, and drug dissolution was determined in vitro.  The pharmacokinetics of crystallized interferon after sc injection in rabbit at 1.5×10⁷ U·kg⁻¹ was compared to that of soluble form.  The crystals were characterized as mono-dispersed spheres, with yield of >80%, mean diameter size of about 16 µm and crystallinity of 23.2%.  The in vitro dissolution behavior of crystallized rhIFN was featured as low initial burst release (21% within the first 2 h) and prolonged cumulative dissolution time up to 72 h without biological potency lost.  After sc administration of soluble and crystallized interferon in rabbits, the peak time (T_max) and half life (t_1/2) were prolonged from (1.80 ± 0.45) h and (1.35 ± 0.35) h to (13.20 ± 2.68) h and (10.68 ± 1.97) h, respectively.  The corresponding peak concentration decreased from (1 411.10 ± 575.28) U·mL⁻¹ to (721.37 ± 206.55) U·mL⁻¹.  PK/PD analysis indicated that (96.87 ± 20.30) % of relative bioavailability was obtained.  The research results of this work will provide important academic value and application prospect for improving clinical therapeutic effect and development of biomacromolecules delivery system for protein and peptide drugs.