Objective To investigate the role of serum inflammatory factors， matrix metallo proteinase （MMP）-9 and soluble CD40 ligand（ sCD40L）， in the pathogenesis and the progression of leukoaraiosis（ LA）. Methods A total of 78 cases of LA patients（ LA group） and 50 cases of healthy physical examination patients （control group） were selected. LA group was divided into 3 grades according to the Fazekas score： 28 cases in mild group， 28 in moderate group and 22 in severe group. The levels of serum MMP-9 and sCD40L were measured by enzyme-linked immunosorbent assay（ ELIAS）， and the cognitive function was evaluated by the Montreal Cognitive Assessment（ MoCA） scale. Results The level of serum MMP-9 and sCD40L of LA group was higher than that of the control group， and the difference was statistically significant（ P＜ 0.05）. With the progression of the disease， the level of serum MMP-9 in LA patients increased gradually， and the difference among different grades was statistically significant（ P＜0.05）. However， there was no significant difference in serum sCD40L among different grades（ P＞ 0.05）. The Pearson correlation analysis showed that the level of serum MMP- 9 was positively correlated with the severity of LA（ r=0.497，P=0.004）， and negatively correlated with MoCA score（ r=-0.398，P=0.030）. There was no significant correlation between the level of serum sCD40L and the severity of LA， the MoCA score（ P＞0.05）. Logistic regression analysis showed that MMP-9 was an independent risk factor for cognitive dysfunction in LA patients（ OR=2.336，P=0.014）. Conclusions Serum MMP-9 and sCD40L are involved in the pathogenesis of LA， and MMP-9 can be used as an indicator to evaluate the severity of LA， which is related to cognitive function.