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Aims: Accumulating experimental and clinical studies provide clear evidence for reversibility of hepatic fibrosis (HF).Apoptosis of activated hepatic stellate cells (HSCs) has proven critical to fibrosis regression, but its mechanisms remain to be clarified.The objective of this study was to validate the apoptotic effect of lignstrazine on rat stellate cells in vitro, and elucidate the molecular mechanisms that underlie this action.Methods: Rat hepatic stellate cells were cultured in vitro.3H-TdR incorporation test and LDH release assay were used to evaluate the anti-proliferative effect of administered ligustrazine in HSCs, and flow cytometry to analyze the apoptotic ratio.Western blotting was performed to determine the expression of three key apoptotic proteins Bcl-2, Bax and caspase-3.Real-time PCR was used to detect their gene expression.Results: HSCs exposed to ligustrazine showed decreased proliferation dose-dependently, and significant apoptosis via a caspase-mediated pathway.Ligustrazine displayed anti-proliferative activity towards HSCs at 50pM and predominant pro-apoptotic effect at 70μM without evident cytotoxicity.Western blotting analysis demonstrated decreased Bcl-2 expression and growing expression of Bax and caspase-3.Real-time PCR experiments indicated that ligustrazine could correspondingly regulate the gene expression of Bcl-2, Bax and caspase-3.Ligustrazine was able to induce HSC apoptosis in rats in vitro depending on a cytochondriome-mediated pathway involving Bcl-2, Bax and caspase-3.Conclusion: This investigation demonstrated the promising role of ligustrazine that may contribute to hepatic fibrosis regression through stimulation of HSC apoptosis.This apoptotic effect was modulated by cytochondriome pathway involving down-regulation of Bcl-2 and up-regulation of Bax and caspase-3 at both gene and protein levels.Elucidation of the underlying mechanisms helped to provide new evidence for drug-facilitated HSC apoptosis.Ligustrazine may be exploited as a potential option for treating and reversing hepatic fibrosis.