Studies demonstrated that pathophysiological abnormalities of airway smooth muscle (ASM) contribute significantly to chronic obstructive pulmonary disease (COPD) pathogenesis, the aim of this study is to investigate heat shock protein 70 (Hsp70) in ASM in COPD. ASM from 8 COPD patients and 6 controls were isolated for detection of Hsp70 using Western blot. Male adult Wister rats were exposed to mixture of cigarette smoke/air or room air for an indicated period. The lung tissues were obtained for pathological analysis, and ASM were dissected for Hsp70 detection. Normalized Hsp70 in ASM from COPD patients was significantly lower than that from controls (P <.001), and it was a significant positive correlation of Hsp70 and lung function. One-month exposure of rats to cigarette smoke/air mixture led to increased expression of Hsp70 and heat shock transcription factor (Hsf1) in ASM as compared to controls, whereas 3-month exposure caused dramatically reduced Hsp70 and Hsf1 than control animals. In addition, 3-month exposure to cigarette smoke/air mixture resulted in significantly lower Hsp70 and Hsf1 in rats ASM than 1-month exposure (P <.001), and it was a positive correlation of Hsf1 and Hsp70. Long-term cigarette smoking results in reduced expression of Hsp70 in ASM. This finding provides additional insight in understanding molecular changes in ASM during COPD pathogenesis.