OBJECTIVE: The present study was designed to evaluate the effect of Adiponectin (APN) against alveolar epithelial apoptosis in chronic obstructive pulmonary disease (COPD) rat models. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley (SD) rats were randomly assigned to three groups: Sham group, COPD group, and COPD + APN group (2.5 ug/kg/day). To assess the effect of APN, histopathological evaluations, lung function, and the apoptotic index (AI) of alveolar septal cells, were performed. In addition, the levels of oxidative stress and endoplasmic reticulum stress were measured. RESULTS: HE staining demonstrated that APN inhibited pathological injury in COPD rats. In addition, APN could restore the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. APN also inhibited the levels of endoplasmic reticulum stress pathway including CHOP, phospho-JNK and Caspase-12 in alveolar epithelial cell. Furthermore, APN significantly inhibited the protein levels of Caspase-3 and apoptosis in alveolar epithelial cell of COPD rats. CONCLUSIONS: Our findings suggested that APN might effectively ameliorate the progression of COPD via inhibiting the endoplasmic reticulum stress-induced alveolar epithelial apoptosis in rats.