Aim To study the inhibitory effect of anti-ErbB2 chimeric antibody chA21 on proliferation of human malignant breast cancer cell lines SKBR3 and explore its possible mechanisms through studying its effects on ErbB2 distribution and PI3K/Akt,Erk1/2 signal transduction.Methods The inhibitory effect of chA21 on SKBR3 was assessed by MTT assay.The effect of chA21 on distribution of ErbB2 on cell plasma membrane was determined by FACS(Fluorescence-activated cell sorting)analysis;p-Akt and p-Erk1/2 were detected by Western blot.Results The inhibitory rate of chA21 on SKBR3 cells in vitro increased in a dose and time dependent manner.Furthermore,it could down-regulate the distribution of ErbB2 on plasma membrane and decrease the activation of p-Akt and p-Erk1/2.Conclusions ChA21 can inhibit the proliferation of SKBR3 cell in vitro.Down-regulation ErbB2 on cell plasma membrane resulting in decreasing the activation of p-Akt and p-Erk1/2 may be one of the mechanisms of the inhibitory effect.