To investigate the effects of the polysaccharides from Spirulina platensis (PSP) on hepatitis B virus (HBV), the cytotoxic effect of PSP was assessed by choosing the maximal concentration of PSP without cytotoxic effect on HepG2 2.2.15 cell line for further experiments. Four concentrations (400-50 μg/ml) of PSP were adopted to treat the cells, and the supernatants or cells were collected after 24, 48, 72 and 144 h respectively. HBsAg and HBeAg in the supernatants of cell cultures were tested with ELISA and copies of HBV DNA in supernatants were measured by real-time fluorescence quantitative PCR (FQ-PCR). Meanwhile, DNA/RNA hybridization was performed to evaluate the expression of IFN-α receptor (IFN-αR) on the cells. The experimental results showed that the secretion of HBV antigens decreased under the influence of PSP in a dose and time-dependent manner. PSP in concentration of 400 μg/ml could significantly decrease the secretion of HBsAg in 24 h. Although no obvious effect was observed on the secretion of HBeAg at that time, the inhibitory effects were observed in a dose-dependent manner from 48 to 144 h. In addition, the copies of HBV DNA were declined under the influence of PSP in the same manner, moreover, the maximal suppressive effect of PSP in concentration of 400 μg/ml was as great as that of lamivudine. The expression of IFN-αR was much higher in PSP-treated cells than that of the un-treated cells also in dose and time-dependent manner. It is concluded that PSP in non-cytotoxic concentration not only significantly decreases the secretion of the HBV antigens and the replication of HBV DNA, but also increases the expression of IFN-αR on HepG2 2.2.15 cell line. The results of the present investigation strongly support the notion that PSP exerts the anti-HBV effect both through enhancing the anti-HBV immunity and acting on HBV directly. To investigate the effects of the polysaccharides from Spirulina platensis (PSP) on hepatitis B virus (HBV), the cytotoxic effect of PSP was assessed by choosing the maximal concentration of PSP without cytotoxic effect on HepG2 2.2.15 cell line for further experiments. Four (400-50 μg / ml) of PSP were adopted to treat the cells, and the supernatants or cells were collected after 24, 48, 72 and 144 h respectively. HBsAg and HBeAg in the supernatants of cell cultures were tested with ELISA and copies of HBV DNA in supernatants were measured by real-time fluorescence quantitative PCR (FQ-PCR). Meanwhile, DNA / RNA hybridization was performed to evaluate the expression of IFN-α receptor (IFN-αR) on the cells. showed that the secretion of HBV antigens decreased under the influence of PSP in a dose and time-dependent manner. PSP in concentration of 400 μg / ml could significantly decrease the secretion of HBsAg in 24 h. bserved on the secretion of HBeAg at that time, the inhibitory effects were observed in a dose-dependent manner from 48 to 144 h. In addition, the copies of HBV DNA were declined under the influence of PSP in the same manner, moreover, the maximal suppressive effect of PSP in concentration of 400 μg / ml was as great as that of lamivudine. The expression of IFN-αR was much higher in PSP-treated cells than that of the un-treated cells also in dose and time-dependent manner It is said that that PSP in non-cytotoxic concentration not only significantly reduces the secretion of the HBV antigens and the replication of HBV DNA, but also increases the expression of IFN-αR on HepG2 2.2.15 cell line. The results of the present investigate strongly support the not that that exerts the anti-HBV effect both through enhancing the anti-HBV immunity and acting on HBV directly.