Objectives: Circulating adiponectin levels in cigarette smokers are lower than those in nonsmokers. We have previously shown that adiponectin is expressed in human monocytes. The aim of this study was to further investigate the effect of smoking on adiponectin expression in peripheral blood mononuclear cells (PBMCs). Methods: A group of 77 cigarette smokers and 51 nonsmokers were consecutively enrolled in this study. The participants' body weight, blood pressure, and metabolic parameters, including plasma glucose and plasma adiponectin levels, were recorded. The RNA from the PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of adiponectin mRNA. Results: Of the 77 smokers, 67 (87.0%) were male. Their mean (standard deviation) age was 43.17 (11.47) years, and they smoked 24.56 (12.53) cigarettes/day. The duration of smoking was 23.73 (11.69) years. Both circulating adiponectin levels (p = 0.0262) and adiponectin mRNA levels in PBMCs (p < 0.0001) of smokers were significantly lower than those in nonsmokers. Both circulating adiponectin levels and adiponectin mRNA levels were negatively correlated with the number of cigarettes smoked per day (p < 0.01). In multiple linear regression analysis, smoking was an independent factor affecting adiponectin mRNA expression in PBMCs (p < 0.0001). Conclusions: Circulating adiponectin levels and adiponectin expression in PBMCs were lower in smokers; this finding suggested that attenuation of both systemic and local actions of adiponectin might contribute to the atherosclerotic process in cigarette smokers.