Cigarette smoking is one of the risk factors for cardiovascular diseases. The objective of this study is to elucidate the molecular mechanism(s) for cell injury induced by unsaturated carbonyl compounds in the gas phase of cigarette smoke. First, the method for preparation of gas phase extract of cigarette smoke was optimized. The cell injury caused by both gas phase extract of cigarette smoke and unsaturated carbonyl compounds was intracellular calcium-dependent. They also activated protein kinase C in intracellular calcium-dependent manner. Several antioxidants such as reduced form of glutathione and vitamin E suppressed cell injury induced by unsaturated carbonyl compounds.