Objective Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3.A growing body of evidence demonstrates that aberrant activity of histone deacetylases or histone acetyltransferase might be an underlying mechanism of transcriptional dysregulation in polyQ diseases including SCA3/MJD, which suggests that the balance of histone acetylation is a good target for therapeutic intervention of polyQ diseases.Some studies have shown a therapeutic role for HDAC inhibitors (HDACIs) as candidate drags for the treatment of polyQ diseases.However, the effects of HDACIs (Hv, confidential now) on models of SCA3/MJD have never been confirmed.The present study is to illustrate the therapeutic potential of Hv in SCA3/MJD transgenic Drosophila models.Methods GAL4/UAS system SCA3/MJD transgenic Drosophila models were constructed by using the promoter gmr-GAL4 and elav-GAL4 which drive target selective gene expression in developing eyes and neurons, respectively.Phenotype observing was used to understand the effect of Hv on the eye morphology, lifespan and climbing ability of SCA3/MJD transgenic Drosophila models.Results The loss of pigmentation and collapse of the eyes of SCA3/MJD transgenic Drosophila models were mitigated by feeding Hv.Their climbing ability was obviously improved especially by dosage of 1 mM or 1.5 mM.Dosage of 0.5 mM could extend their lifespan.Conclusions SCA3/MJD transgenic Drosophila models were successfutly constructed, which selectively express human MJDtr-Q78 protein with different levels in developing eyes or neurons respectively.It was further confirmed that the expression level of MJDtr-Q78 protein are concerned to the severity of SCA3/MJD symptoms.It was also found that proper dosage of Hv has therapeutic potential in these models.