Diffuse malignant pleural mesothelioma is a disease with poor prognosis, and no standard therapy for inoperable cases has been established. There are several reported trials using various anticancer drugs, but their sample sizes were small and none documented the drugs' effectiveness. Recently, some reports revealed that gemcitabine (GEM), which has been demonstrated to be effective for the treatment of non-small cell lung carcinoma, was effective in cases of diffuse malignant pleural mesothelioma. We also treated a 76-year-old female patient with inoperable, biphasic malignant pleural mesothelioma in whom monotherapy with GEM 1,000 mg/m2 was continued leading to improved QOL and survival for 2 years. Though diagnostic imaging indicated SD (stable disease), a high efficacy was observed in terms of reduced subjective symptoms such as a feeling of difficulty in breathing and pain. It is suggested that GEM is a potentially effective drug for the improvement of QOL in inoperable cases of diffuse malignant pleural mesothelioma.