Background:　Imbalance　between　protease-antiprotease　plays　an　important　role　in　the　pathogenesis　of　chronic　obstructive　pulmonary　disease　(COPD).　Cystatin　C　in　circulating　blood　is　a　cysteine　protease　inhibitor　and　contributes　to　elastolysis　and　tissue　destruction.　Objectives:　The　aims　of　the　present　study　were　to　investigate　whether　cystatin　C　was　a　promising　biomarker　for　the　evaluation　and　follow-up　of　patients　with　COPD.　Methods:　Serum　cystatin　C　level　was　determined　in　groups　of　acute　exacerbation　of　chronic　obstructive　pulmonary　disease　(AECOPD)　(n　=　93),　stable　COPD　(SCOPD)　(n　=　299)　and　healthy　controls　(n　=　151).　The　influences　of　smoking　on　the　level　of　serum　cystatin　C　and　the　correlation　of　cystatin　C　with　lung　functional　parameters　were　further　analyzed.　Results:　Serum　cystatin　C　level　was　significantly　higher　in　COPD　patients　than　that　of　healthy　controls.　Smoking　increased　serum　cystatin　C　level　in　patients　with　SCOPD　but　not　in　AECOPD　and　control.　In　SCOPD　group,　serum　cystatin　C　level　was　positively　correlated　with　RV%TLC　and　negatively　correlations　with　FEV1%　predicted,　FEV1%FVC,　MMEF75/25%　predicted,　MVV%　predicted　and　DLco%　predicted.　In　multiple　line　analysis,　FEV1%　predicted　and　age　were　found　to　be　independent　predictors　of　serum　cystatin　C　levels,　but　not　smoking　statue,　sex　and　BMI.　Conclusions:　COPD　had　a　higher　level　of　serum　cystatin　C,　smoking　only　increased　cystatin　C　level　in　SCOPD.　Serum　cystatin　C　level　was　negatively　correlated　with　FEV1%　predicted.　These　results　suggest　that　cystatin　C　might　be　a　potential　biomarker　for　lung　tissue　destruction　and　severity　of　COPD.