Berberine, the main isoquinoline alkaloid obtained from traditional plants, e.g. , Berberis , Coptis , Coscinium spps., etc. , is known to exhibit anticancer activity in vitro and in vivo . In this study, the anticancer potential of berberine combined with PEGylated liposomal doxorubicin (polyethylene glycol (PEG)-lip-DOX) was investigated. At first, the effect of berberine on endothelial cells was examined in vitro by use of human umbilical vein endothelial cells (HUVECs): Berberine inhibited HUVEC growth with an IC₅₀ at 24 h of about 144 µg/mL and that at 72 h of about 29 µg/mL. In contrast, less than 50 µg/mL berberine inhibited the vascular endothelial growth factor (VEGF) expression to some extent after a 24-h incubation, suggesting that berberine suppressed angiogenic action under the condition of little cytotoxicity. Next, the in vivo anticancer activity of the combination of berberine (intraperitoneally (i.p.)) and PEG-lip-DOX (intravenously (i.v.)) was examined in Meth A sarcoma-transplanted BALB/c mice. The results showed that either berberine or PEG-lip-DOX exhibited antiproliferative activity against Meth A cells. Moreover, treatment with the combination of berberine and PEG-lip-DOX suppressed the tumor growth more strongly than that with berberine or PEG-lip-DOX alone. Based on these findings, the combination cancer chemotherapy with berberine and PEGylated liposomal doxorubicin may be beneficial for the treatment of cancer.