Objective To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-kappa B inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). Methods Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNF alpha-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants. Results It was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNF alpha for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNF alpha for 24 h. The stimulatory effect of TNF alpha just on proMMP-9 was counteracted significantly by CAPE. Conclusion NF-kappa B could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNF alpha (a pro-apoptotic factor). Therefore, therapeutic NF-kappa B inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.