Objective：To investigate the protective effect of activated AMP-activated protein kinase （AMPK） on the human umbilical vein endothelial cell（HUVEC） damage induced by palmatlc acid （PA） and the related mechanism. Methods： HUVEC were divided into 8 groups according to the culture media （cultured for 24 to 72 h）： blank control （conventional culture）, 300 μmol/L PA, 1 mmol/L aminoimidazole-4-carboxamide-l-beta-ribofuranoside （AICAR）, PA＋ AICAR, 2 mmol/L metformin, PAq-metformin, 10 btmol/L pioglitazone, and PAq-pioglitazone groups. Survival rates of HUVEC were determined by MTT at 24, 48 and 72 h after culture. Western blot were performed to detect the expression of phospha-AMPK at 24 h after culture. Results： Compared with blank control group, cell survival rates in PA group were decreased by 58.95M, 36.68% and 15.09M at 24, 48 and 72 h（P〈0.05）, respectively. Seventy-two hours after culture, HUVEC survival rates of AICAR-t-PA group, Metnt-pA group and PGZ＋PA group were obviously higher than that of PA group （P〈0.05） ; AICAR, metformin or pioglita- zone alone had no obvious influence on HUVEC survival rate. Twenty-four hours after culture, Phospha-AMPK expression was increased in AICAR, metforrnin and pioglitazone groups compared with that of control group （P〈0.05）. Conclusion： AICAR, metformin and pioglitazone can decrease the damage of HUVEC induced by PA, possibly through activating AMPK