A 45-year-old woman complaining of exertional dyspnea consulted at our hospital because of massive left pleural effusion, which contained many plasma cells with elevated adenosine deaminase (ADA) levels. No malignant cells were detected in pleural effusion. The condition progressed rapidly within only three weeks and was removed by chest drainage. Computed tomography scans of the chest showed enhanced pleural thickenings and nodules. A pathological examination of the biopsied specimen obtained by video-assisted thoracoscopic surgery showed nonspecific pleurisy with plasma cell infiltration in the pleura and arterial walls. The antinuclear antibody test result was positive, double-stranded deoxyribonucleic acid specific antibody levels were elevated, and the serum complement titer was decreased. Therefore we diagnosed the patient with systemic lupus erythematosus (SLE) accompanied by pleurisy and pleural effusion. We described an interesting case of SLE with massive and rapidly progressive unilateral pleural effusion containing many plasma cells with elevated ADA levels at the initial presentation.