objective: nitric oxide produced by endothelial nitric oxide synthase (enos) possesses multiple anti-atherosclerotic properties. hence, enhanced expression of enos and increased nitric oxide levels may protect against the development of atherosclerosis. piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. this study aimed to investigate the effects of piper sarmentosum on the enos and nitric oxide pathway in cultured human umbilical vein endothelial cells (huvecs). methods: huvecs were divided into four groups: control, treatment with 180 μm hydrogen peroxide (h2o2), treatment with 150 μg/ml aqueous extract of piper sarmentosum, and concomitant treatment with aqueous extract of ps and h2o2 for 24 hours. subsequently, huvecs were harvested and enos mrna expression was determined using qpcr. the enos protein level was measured using elisa, and the enos activity and nitric oxide level were determined by the griess reaction. results: human umbilical vein endothelial cells treated with aqueous extract of piper sarmentosum showed a marked induction of nitric oxide. treatment with ps also resulted in increased enos mrna expression, enos protein level and enos activity in huvecs. conclusion: aqueous extract of piper sarmentosum may improve endothelial function by promoting no production in huvecs.