Objective：To study the influence of multiple myeloma cells（MMCs）on the secretion of tissue-type plasminogen activator（tPA）and tissue-type plasminogen activator（PAI-1）by the cultured human umbilical vein endothelial cells（HUVEC）to confirm the fibrinolytic activity as well as the causes and mechanisms of thrombosis in multiple myeloma（MM）. Methods：Human MM cell line U266 was co-cultured with HUVEC for 24 h，48 h and 72 h，with the same period of HUVEC cultured alone as control as well as MMCs. The expressions of HUVEC，MMCs tPA，and PAI-1 mRNA in those groups were detected by polymerase chain reaction（PCR），tPA and PAI-1 protein levels in the supernatant were detected by ELISA. Results：No expression of tPA and PAI-1 protein and mRNA in the culture supernatants of MMCs was detected by both ELISA and PCR. The expression level of tPA protein in the co-culture system by ELISA was significantly（P < 0.05）higher than that in the control group，as well as the PAI-1 protein level（P < 0.05）. There was a positive correlation between the PAI-1 and tPA protein level in the control group（rs=0.80，P=0.01）and in the co-culture system（rs=0.88，P=0.002）by ELISA. The levels of t-PA and PAI-1 protein were positively correlated with the time in the HUVEC cultured alone group（rs=0.90，P=0.001；rs=0.90，P=0.001）and the co-culture system（rs=0.95，P＜0.001；rs=0.84，P=0.004）significantly by ELISA. The difference of the expression level of tPA mRNA between the two groups was not significant（P > 0.05），as well as the expression level of PAI-1 mRNA（P > 0.05）. Conclusion：MMCs can promote the secretion of tPA and PAI-1 protein from HUVEC. On the premise of ensuring the cells viability，the secretion of both proteins increased along with the extension of incubation time，and there was a certain correlation between the tPA and PAI-1 protein level. However，MMCs had no obvious effect on the expression level of tPA and PAI-1 mRNA.