In order to study sub-acute hepatotoxicity of low doses of microcystins in vivo, as well as to understand the mechanisms of hepatotoxicity of microcystins, eighty Spague-Dawley rats were injected with microcystins intraperitoneally at the doses of 0, 4, 8 and 12 micrograms.(kg.d)-1, respectively, for 35 days. Then blood and liver samples were used for assay. Several enzymatic levels and pathological changes were detected. Both terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and immunohistochemical methods were employed to study the apoptosis and proliferating cell nuclear antigen (PCNA). It was shown that the activity of serum gamma-glutamyltransferase (GGT) and concentrations of whole blood glutathione (GSH) decreased, serum activities of lactate dehydrogenase (LDH) and aminotransferase (AST) increased after exposure to MC. No significant change of concentration of serum alanine aminotransferase (ALT) was observed in the tested groups. Characteristic morphological alterations and active proliferation as well as apoptosis of hepatotocytes were observed in the treated groups. It was suggested that oxidative injury and apoptosis of hepatocytes induced by microcystins may be the mechanisms of its hepatotoxicity.