Abstract Background Airway inflammation plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Endogenous hydrogen sulfide (H 2S) is involved in the physiological and pathophysiological process in systemic inflammation and may be involved in the pathogenesis of airway inflammation and airflow obstruction in COPD. The non-selective phosphodiesterase inhibitor theophylline has bronchodilator/anti-inflammatory properties and is widely used in the treatment of airways diseases. It is not fully understood whether endogenous H 2S mediates the mechanism of theophylline anti-inflammatory effect. Methods The effect of short-term theophylline treatment on airway inflammation and endogenous H 2S production was prospectively studied in thirty-seven patients with stable COPD. Patients were randomly divided into theophylline-treatment group (nineteen patients, orally given sustained theophylline tablets for 1 month, 0.2 g, q12h) and control group (eighteen patients, not given any theophylline). Symptom score, lung function, total and differential cell counts in sputum, serum H 2S and nitric oxide (NO x ) levels, sputum and serum IL-8 levels were measured at baseline and 1 month later. Results No significant difference was found in symptom scores, lung function and other investigated experimental parameters at baseline between treatment and control groups, and between baseline and a month follow-up in control patients. Symptom scores were significantly lowered only in the treated patients after treatment, compared with those before ( P<0.01). The proportion of neutrophils in sputum was significantly decreased ( P<0.05) while that of macrophages was markedly increased ( P<0.01) in the treated patients after treatment, compared with that before. No significant change was found in serum H 2S and NO x levels, serum and sputum IL-8 levels before and after experiment in treatment group. Serum H 2S level correlated positively with percentage of predicted FEV 1 ( r=0.465, P=0.005), and with proportion of sputum macrophages ( r=0.349, P=0.05), but negatively with proportion of sputum neutrophils ( r=−0.351, P=0.049) in all patients at baseline. Conclusions Short-term theophylline treatment improved symptoms and decreased sputum neutrophils in COPD, while serum H 2S levels were not affected in our study population. Large samples will be needed to illustrate the effect of long-term theophylline treatment on inflammatory mediators and H 2S generation in COPD.