Background : Platelet can release lots of active molecules from granules in active state, which contributes to the progress of atherosclerosis and thrombosis. Fruitflow is a water-soluble tomato extract that has been reported to exert protective cardiovascular effects. The present study aims to investigate whether Fruitflow acts on human platelet granule secretion in vitro and further explore its underlying mechanisms. Methods: Recruit healthy volunteers to collect their peripheral blood and isolate gel-filtered platelets for in vitro experiments. Agonist-induced platelet granule secretion was detected by flow cytometry or ELISA kit. To elucidate the molecular mechanisms, the signaling pathway was tested by western blotting. Results: Fruitflow inhibited platelet surface expression of CD62P, CD40L, and CD63. Moreover, agonist-induced release of platelet factor 4 (PF4), β-thromboglobulin (β-TG), Regulated on Activation Normal T cell Expressed and Secreted (RANTES), transforming growth factor-β1 (TGF-β1), ATP, Ca 2+ , and serotonin were also significantly attenuated by Fruitflow. Furthermore, Fruitflow down-regulated expression of Lyn and phosphorylation of Src, LAT, Syk, PLCγ2 and PKC. However, PKC inhibitor GF109203X did not show additive effects on platelet granule secretion when combined with Fruitflow. Conclusion: Fruitflow effectively inhibited platelet granule secretion via down-regulating platelet Src/PLC-γ2/PKC signaling pathway in vitro , which may provide a novel evidence for the cardioprotective benefits of tomato.