Aim To study the inhibitory effect and mechanisms of Momordicin on foam cell. Methods Momordicin (28 kDa) was purified from the juice of Momordica charantial by eccentricity, super-filtration and chromatography technology. After incubated with 160 nmol/L PMA for 24 h, THP-1 was induced to macrophage, this macrophage was induced to foam cell by incubated with 25 mg/L ac-LDL for 48 h, and the effect of Momordicin on foam cell was measured, cholesteryl and cholesteryl ester within THP-1 were measured by high performance liquid chromatography (HPLC), and regulated effect of Momordicin on ATP binding cassette transporter A1 (ABCA1) was measured by RT-PCR. Results A positive inhibitory effect of Momordicin on foam cell was found. Total cholesterol (TC) and cholesteryl ester (CE) were reduced remarkably by Momordicin(p<0.01), CE/TC was reduced from 62.9% to 36.2% by Momordicin, ABCA1 was up-regulated by Momordicin (P=0.035) remarkably. Conclusions The inhibitory effect of Momordicin on foam cell may related to it's activity of up-regulating ABCA1.