OBJECTIVE：To study inhibitory effect of Lycianthes biflora polysaccharide on the proliferation of hepatic stellate HSCs-T6 cells in rats and its mechanism. METHODS：After treated with 0（blank control），50，100，200 μg/ml L. biflora polysaccharide for 24 and 48 h，the activity of hepatic stellate HSCs-T6 cells in rats was determined by MTT assay and inhibitory rate of cell proliferation was calculated；the content of Hyp in supernatant was detected by immunohistochemical assay. After 48 h，the expression of cellular α-smooth muscle actin（α-SMA）was measured by immunohistochemical assay；both transforming growth factor β1（TGF-β1）and Smad3 were measured by Western blot assay. RESULTS：Compared to blank control，50，100 and 200 μg/ml L. biflora polysaccharide could inhibit the proliferation of HSCs-T6 cells；cell inhibitory rates were 39.84％-69.31％ and 45.16％-82.93％ respectively after treated for 24 and 48 h，which were positively associated with time and concentration. The contents of Hyp in supernatant were 178.36-93.25 μg/ml and 131.94-68.74 μg/ml respectively after treated with different concentrations of PRP for 24 and 48 h，which were negatively associated with time and concentration. The protein level of TGF-β1 and Smad3 decreased after treated with L. biflora polysaccharide for 48 h（P＜0.01）. CONCLUSIONS：L. biflora polysaccharide can inhibit the proliferation of hepatic stellate HSCs-T6 cells in rats，and its mechanism is associated with the inactivation of endogenous TGF-β pathway for reducing collagen production.