Chronic obstructive pulmonary disease (COPD) is a systemic disease characterized by chronic, progressive airflow limitation and airway inflammation. In this study, our aim is to compare the effects of inhaled corticosteroids and theophylline on systemic inflammatory markers in COPD. Twenty-nine moderate to severe COPD patients were randomly separated into two groups. In Group 1, inhaled corticosteroids (fluticasone propionate, 1000 meg/day) were added to regular bronchodilator therapy for 8 weeks, and theophylline (400mg/day) was added in Group 2. Pulmonary function tests were performed and serum CRP, TNF-α, and IL-6 levels were measured before and after treatment. There was a statistically significant decrease in serum CRP levels in both groups following treatment (ICS group 1.06±1.2 vs 0.49±0.22 mg/dl p< 0.05; THEO group 1.66±2.23 vs 0.59±0.35 mg/dl p< 0.05). There was a significant reduction in serum TNF-α levels in the THEO group (3.82±3.44 vs 1.89±1.33 pg/ml p< 0.05). There was no significant change in IL-6 level following treatment in either group. There was a significant increase in FEV₁ in the ICS group while a non-significant increase was noted in the THEO group following treatment. It has been suggested that both ICS and THEO could be used as an anti-inflammatory agent in the treatment of COPD. Furthermore, the measurement of serum inflammatory markers is an easy and non-invasive method for the determination and follow-up of systemic inflammation in COPD. Further studies including larger patient population are needed.