Green tea polyphenols (GTP) have been shown to possess anti-oxidative, anti-mutagenic and anti-carcinogenic activities. The present study aimed to evaluate the chemopreventive efficacy of GTP against subacute hepatotoxicity induced by microcystin-LR (MC-LR) in mice and also elucidates the underlying mechanisms. In this study, healthy Kunming male mice (24-26gbw) were randomly assigned to five groups. Group I was fed on normal diet and water ad libitum as control. Group II was maintained on normal diet and received MC-LR intraperitoneal injection (10μg/kg/day) from day 6 till sacrifice. Mice in groups III, IV and V were daily pre-treated with GTP through intragastric administration at doses of 50, 100 and 200mg/kg/day from day 0 prior to MC-LR intoxication, consecutively 18 days. The results showed MC-LR alone led to oxidative stress and to damage antioxidant defense system, as evidenced by elevation of serum and liver lipid peroxidation. Additionally, hepatocellular apoptosis and injury were significantly observed. GTP pre-treatment caused a significant elevation in serum antioxidant enzymes GSH and SOD activities as well as a decrease in hepatic lipid peroxidation MDA level and serum ALT, AST, ALP activities. GTP pre-treatment obviously inhibited hepatocellular apoptosis and up-regulated Bcl-2 protein expression. The damages in liver were less severe in GTP pre-treated mice in correlation with the biochemical parameters. In summary, this study confirmed that repeated exposure to MC-LR could induce hepatotoxicity. Our study demonstrated that GTP can reduce MC-LR-induced oxidant stress and prevent biochemical parameters and pathological changes caused by MC-LR in a dose-dependent manner. The results indicated that tea polyphenols have a potential to be developed as a preventive agent against MC-LR-induced toxicity and the mechanism involved in the protection could be due to their antioxidant activities.