Background: Previous studies have demonstrated that alterations in certain circulating biomarkers may be correlated with Coal workers' pneumoconiosis (CWP). This study investigated the relationship between changes of serum biomarkers and pulmonary function during the development of CWP. Methods: Lung function parameters and specific serum indices were measured in 69 non-smoking coal workers, including 34 miners with CWP, 24 asymptomatic miners and 11 miners with minimal symptoms. The associations between changes in pulmonary function and serum indices were tested with Pearson's correlation coefficients. Multivariable analysis was used to estimate the predictive power of potential determinant variables for lung function. Results: Compared to healthy miners, lung function (FVC, FEV1, FEF50, FEF75, FEF25-75 % of predicted values) was decreased in miners with CWP (p < 0.05). Increased serum matrix metalloproteinase-9 (MMP-9) was associated with decreased FVC% of predicted values in the asymptomatic miners (r = -0.503, p = 0.014). Conclusions: In coal mine workers, alterations of lung function parameters are associated with the development of CWP and with changes in circulating MMP-9, TIMP-9, IL-13 and IL-18R. These serum biomarkers may likely reflect the pathogenesis and progression of CWP in coal workers, and may provide for the importance of serum indicators in the early diagnosis of lung function injury in coal miners.