Abstract: AIM: To study the effect of CD40L and matrix metalloproteinases on coronary artery restenosis after coronary artery stent interpolation (CASI) and to evaluate the prognosis of CASI by measuring the hematology level of CD40L and matrix metalloproteinases. METHODS: Three hundred and thirty patients with coronary artery disease received CASI, 186 were male and 144 female (average age was 69.4 years). Hematology levels of CD40L, CRP, MMP-2 and MMP-9 of all 330 patients were measured by enzyme-linked immunosorbent assay (ELISA), respectively, before and 1 and 6 months as well as 1 year after CASI. According to CSA criteria, 32 cases of coronary artery restenosis after CASI were classified into group one, group two and group three. RESULTS: Compared with the values before the interventional therapy, hematology levels of CD40L, CRP, MMP-2 and MMP-9 among the selected patients, without exception, decreased significantly 1 month, 6 months and 1 year after CASI. In the cases of post-CASI coronary artery restenosis, the previously mentioned corresponding items increased evidently, and the values were positively correlated with CSA grade and severity of CAD. CONCLUSION: CD40L and MMPs are related to coronary artery restenosis after CASI. CD40L may injure the coronary artery a second time through MMPs and thus result in the formation of atheromatous plaques. The measurement of hematology levels of CD40L and MMPs are of some value in predicting the prognosis of CASI.