The NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multi-protein complex, produces the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which may contribute to the development of airway inflammation in chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the correlation between circulating and local airway NLRP3 inflammasome activation with acute exacerbation of COPD (AECOPD). mRNA levels of NLRP3, Caspase (Casp)-1, apoptosis-associated speck-like protein containing CARD (ASC), IL-18, and IL-1β in peripheral blood mononuclear cells (PBMCs) and bronchial tissues were determined by real-time PCR in 32 smokers, 65 patients with AECOPD, 50 COPD patients in recovery stage, and 30 COPD patients in stable stage. The levels of IL-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) supernatants were measured by ELISA. The load of six common pathogens in BALF samples were determined by real-time PCR. The potential correlation between the mRNA levels of NLRP3, Casp-1, ASC, IL-18 or IL-1β and the load of pathogens was evaluated individually. Significantly higher mRNA levels of NLRP3, Casp-1, ASC, IL-18, IL-1β and higher levels of IL-18 and IL-1β were found in patients with AECOPD than in smokers. These NLRP3 inflammasome mediators were significantly decreased when COPD patients in the same group became clinical stable. The increased mRNA levels of NLRP3 inflammasomes in bronchial tissues were positively correlated with the load of the six common pathogens in the lower respiratory tract. We conclude that systemic and local airway NLRP3 inflammasome activation is associated with the acute exacerbation, which might be predictive factors of the acute exacerbation and clinical outcomes in COPD patients.