Vessel injury provokes a release in proinflammatory cytokines that influence vascular smooth muscle cell (VSMC) proliferation. The purposes of this study was to determine the effects of recombinant human interleukin-10 (rhIL-10) on rat vascular smooth muscle cell proliferation and the activity of p44/p42 mitogen-activated protein kinase (MAPK) promoted by tumor necrosis factor-alpha (TNF-alpha). Rat aortic VSMCs were cultured and treated with rhIL-10 or TNF-alpha respectively, and then cotreated with rhIL-10 and TNF-alpha. The proliferation of VSMCs was quantified by colormetric assay. Cell cycle analysis was performed by flow cytometry. The p44/42 MAPK activity was evaluated by the immunoblotting technique using anti-p44/42 phospho-MAPK antibody. Compared to control group, TNF-alpha stimulated significantly VSMC proliferation in TNF-alpha group. rhIL-10 alone had no effect on VSMC growth, but significantly inhibited VSMC proliferation induced by TNF-alpha at a dose of 10 ng/ml. The cell number in G(0)/G(1) phase of TNF-alpha and rhIL-10 co-treatment group was higher than that of TNF- alpha group (P<0.01) by flow cytometry analysis. The p44/42 MAPK activity was significantly enhanced by TNF-alpha and the TNF-alpha effect was opposed by rhIL-10. It is suggested that rhIL-10 can inhibit TNF-alpha induced VSMC proliferation and phosphorylation of p44/42 MAPK.