Chronic underlying inflammation is involved in the pathophysiology of coronary artery disease (CAD). Polyalthia longifolia var. pendula bark extract (PLE) is known to exhibit anti-inflammatory activity and has high content of phytosteroids. Since phytosteroids mimic estrogen structurally, we postulated that PLE may provide protection in postmenopausal women against CAD. Thus the effect of PLE has been explored on expression of estrogen receptors (ERalpha and ERbeta) and inflammatory inducible nitric oxide synthase (iNOS) genes in vitro in peripheral blood mononuclear cells (PBMCs) obtained from postmenopausal women. A total of 20 postmenopausal women were included in the present study. Group I (N = 10) included women with angiographically proven CAD, and group II (N = 10) is composed of equal number of age-matched healthy postmenopausal females as controls. Significantly low levels of serum 17-beta estradiol were observed in subjects of group I as compared to group II (p < 0.01). A marked increase in L: -citrulline levels (p > 0.05) and significantly augmented levels of reactive nitrogen intermediates (p < 0.05) were observed in group I subjects. PLE significantly attenuated PMA-induced expression of both ERalpha and ERbeta receptors and inflammatory iNOS gene in vitro in a dose- and time-dependent manner and had an additive effect on these genes when compared with tamoxifen. Ours is the first report to demonstrate that PLE contains certain bioactive principles, which possess anti-inflammatory and estrogenic properties, and thereby hold the promise to be screened for their anti-atherogenic potential in experimental animals to favorably alter several other markers of cardiovascular risk.