Abstract： AIM　To investigate the inhibitory effects of D-polymannuronic sulfate (DPS) on the proliferation of rat vascular smooth muscle cells (VSMC) induced by basic fibroblast growth factor (bFGF) or interleukin-1 (IL-1) and its related mechanisms. METHODS　Rat aortic smooth muscle cells pretreated with DPS in concentrations ranging from 0.001 μg*mL-1 up to 100 μg*mL-1 were incubated at 37℃ for 24 h, followed by addition of bFGF (50 ng*mL-1) or IL-1 (50 U*mL-1) for another 24 h. The effects of DPS on the proliferation of VSMC were evaluated by MTT assays. VSMC were pretreated with DPS in concentrations ranging from 0.001 μg*mL-1 up to 1 μg*mL-1, followed by addition of L-NAME (0.1 μg*mL-1) or bFGF (50 ng*mL-1) for 24 h. Supernatant nitric oxide (NO) was determined with NO assay kit, while supernatant angiotensin II (Ang II) and endothelin-1 (ET-1) were measured by radioimmunoassay. RESULTS　DPS exerted antiproliferative effects at concentrations ranging from 0.01 μg*mL-1 to 10 μg*mL-1, and its maximal effect was observed at the concentration of 1 μg*mL-1. Also, the suppressing actions of DPS on the proliferation of VSMC were diminished by increasing the concentrations of bFGF or IL-1. Furthermore, DPS increased NO synthesis and decreased Ang II and ET-1 contents released from VSMC in a concentration-dependent manner. CONCLUSION　DPS afforded the antiproliferative effects on bFGF- or IL-1-treated VSMC and its underlying mechanisms were associated with enhancement of NO synthesis and decrement of Ang II and ET-1 production/release in vitro.