Activation of STAT3 was inhibited by berberine in vivo . Mice were continuously treated with saline (control group), low dose of berberine (5 mg/kg) and high dose of berberine (10 mg/kg) for every other two days up to a period of 43 days. The mice were then sacrificed and the tumors were sectioned and detected for p-STAT3. The sections were also stained with cytokeratin antibodies to identify the C666-1 cells from the fibroblasts. 5 random microscopic fields which consist of more than 95% of C666-1 cells were chosen for examination. Both low and high dose of berberine could significantly suppress the activation of STAT3 (p < 0.05) in C666-1 cells when compared to the controls.