Gaucher disease is an autosomal recessive lysosomal storage disorder resulting in a deficiency of glucocerebrosidase (GC). Imiglucerase, a recombinant form of GC, has been successfully used in the treatment of Gaucher disease and has been shown to be a good potential candidate for gene therapy. However, its low transduction efficiency and short duration of expression have limited it as a gene therapy strategy. VP22, the herpes simplex virus type I tegument protein, is known to facilitate intercellular protein transport, thus making it a promising tool for improving gene transfer efficiency. To investigate whether the fusion of VP22 to GC could improve its therapeutic efficiency for Gaucher disease, the lentiviral vectors pHIV-GC and pHIV-VP22-GC were constructed and confirmed by PCR or RT-PCR. After packaging, the vectors were transduced into human Gaucher II fibroblast cells (GII cells). Flow cytometric analysis revealed that the GC expression rates in lenti-VP22-GC-transduced GII cells were higher by comparison than those in lenti-GC-transduced GII cells. A Western blot demonstrated higher levels of GC protein expression in lenti-VP22-GC-transduced GII cells. In addition, the long-term expression levels and increased GC activities in lenti-VP22-GC-transduced GII cells were also observed. These data implicate that VP22-mediated effects may be useful for enhancing the efficacy of this Gaucher disease treatment.