A 48-year-old Japanese man who had received sodium valproate (VPA) and carbamazepine since he was 8 years old to treat his secondary epilepsy resulting from cerebral palsy presented with a moderate-sized right pleural effusion. He was admitted to our hospital for diagnosis and treatment and had no history of allergic diseases or hypersensitivity to drugs. He was diagnosed with pleuritis caused by a suspected bacterial infection and was treated with intravenous antibiotics by 6 g per day of sulbactam/ampicillin and 200 mg per day of minocycline. However, the pleural effusion did not decrease. The pleural fluid contained 54% eosinophils, but showed no evidence of bacterial or mycobacterial infection or of the presence of malignant cells. We excluded parasitic infection, pneumothorax, pulmonary embolism, asbestosis, and collagen diseases. We diagnosed VPA-induced pleuritis because the pleural effusion decreased after the VPA dose of 1,200 mg per day was halved and increased when the full-dose of VPA was readministered.