Objective To investigate the effects of endothelial cell, neutrophil and platelet activation on the development and thrombophilia of malignant lymphoma. Methods The levels of cell activating factors soluble thrombomodulin (sTM) in 40 patients with malignant lymphoma and 30 healthy controls in Jiangdu People ''s Hospital of Yangzhou from October 2009 to November 2016 were tested by enzyme linked immunoabsorbent assay (ELISA). The flow cytometry (FCM) method was used to measure the level of CD11b on the surface of anti-freezing whole blood neutrophil and CD62p on the surface of platelet. The results were analyzed by ANOVA and LSD-t test. Results The level of sTM in patients with malignant lymphoma before treatment was significantly higher than that after treatment and in the control group [(49.7±9.3) ng/ml vs. (6.3± 1.8) ng/ml, (5.6±1.5) ng/ml respectively;F=736.633, P=0.000]. There were significant differences between the levels before and after treatment and before treatment and in the control group (t= 33.789, P= 0.000;t=31.782, P=0.000). The average fluorescence intensity (MFI) of neutrophil surface CD11b in patients with malignant lymphoma before treatment was significantly higher than that after treatment and in the control group (184 ± 43 vs. 118 ± 12, 112 ± 15 respectively; F=101.845, P=0.000). There were significant differences between the levels before and after treatment and before treatment and in the control group (t=12.228, P= 0.000; t= 12.184, P= 0.000). The level of platelet surface CD62p in patients with malignant lymphoma before treatment was significantly higher than that after treatment and in the control group [(6.4 ± 2.4) ％ vs. (1.2 ± 0.7) ％, (1.3 ± 0.5) ％ respectively; F= 141.481, P= 0.000]. There were significant differences between the levels before and after treatment and before treatment and in the control group (t=15.010, P= 0.000; t= 13.679, P= 0.000). Conclusions The levels of cell activating factors might be correlated with the progression of malignant lymphoma. Furthermore, endothelial cell, neutrophil and platelet activation have accelerated the development of malignant lymphoma, and the interaction among them may result in the prethrombotic state.