Abstract: There were accumulating evidences that relate the occurrence of atherosclerosis and inflammation in the intima of arteries. Atherosclerosis itself has been known as chronic inflammatory disease. Many signaling molecules such as ICAM-1, VCAM-1, MCP-1, M-CSF and NO have been found in the atherosclerotic plague of the arteries in heart disease patients. This study aimed to investigate the effect of Tinospora crispa Aqueous Extract (TCAE) and Methanol Extract (TCME) on Tumor Necrosis Factor (TNF)-α induced inflammation on Human Umbillical Vein Endothelial Cells (HUVECs) in vitro. HUVECs were cultured on 6 wells plate before been treated by TCAE and TCME at various concentrations (100, 200, 400 and 600 μg mL-1). After 1 h of incubation, TNF-α (10 ng mL-1) was exposed on HUVECs. HUVECs were harvested after 24 h and tested for ICAM-1, VCAM-1, M-CSF and NO using kit. Results of this study indicated that TCAE and TCME exert inhibitory effect on TNF-α induced secretion of ICAM-1, VCAM-1 and M-CSF signaling molecule while NO secretion was increased. These results showed that T. crispa extracts has inhibitory effect in vitro on the level of inflammatory signaling molecules thus it may have a potential benefits on the development of nutraceuticals in the prevention of atherosclerosis-related cardiovascular diseases.