Volume regulated anion channels (VRACs) are involved in regulating the proliferation and cell cycle progression of a number of cell types.However, little is know about its role on astrocytes proliferation although numerous VRACs were reported to play important roles in astrocytic neurotransmitters release during swelling.In the present study, we demonstrated that VRACs inhibition by DCPIB can attenuate the astrocytes proliferation and DNA synthesis in vitro.Simultaneously, Western blots showed that VRACs inhibition led to a decrease in cdk4, cyclinD1expression accompanied with an increase in p27 expression, which caused the proliferating astrocytes arrested at G1/S checkpoint.Furthermore, we showed that DCPIB induced astrocyte proliferation inhibition was modulated through the ERK signaling cascade.These observations demonstrated that VRACs play essential roles in the proliferation of astrocyte.