Objective：To evaluate the influence of rhCD40L on mononuclear macrophage, U937 cells, secreting matrix metalloproteinases （MMPs） and its possible mechanism. Methods： U937 cells were treated with different concentrations of rhCD40L and NS-398 （specific antagonist of COX-2） for 24 h and the supernatants were harvested. Cells treated with 0.4 μg/ml rhCD40L were further treated with 10^-4 mol/L NS-398 or aspirin separately for 24 h and the supernatants were harvested. Zymography was used to determine the activities of MMPs in the above supernatants. Results： rhCD40L increase the activity of MMP-2 and MMP-9 in a dose-dependent manner （P〈0.01） ; the increased peaked when rhCD40L was at 0.4 μg/ml. NS-398 inhibited the activity of MMP-2 and MMP-9 in a dose-dependent manner （P〈0.05）. NS-398 and aspirin both significantly inhibited the activity of MMP-2 and MMP-9 induced by rhCD40L （P〈0.05）. Conclusion： rhCD40L can induce U937 cells to secrete MMPs in a dose dependent manner, which might be related to COX, more possibly through COX-2 than COX-1 pathway