Leflunomide (LEF) is an isoxazole derivative used as disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA). It is effective and safe in patients with active RA, in whom standard treatment is insufficient or contraindicated, but it can cause interstitial lung disease (ILD). Identified risk factors for LEF-induced ILD include pre-existing ILD, cigarette smoking, low body weight, and use of loading dose. LEF should be avoided in patients with pre-existing ILD. We present a case of 59-year-old male with RA and a history of smoking and methotrexate (MTX) treatment, who developed dyspnoea, non-productive cough, and fever about two months after the administration of LEF. The clinical and radiological presentation was of acute pneumonia. The patient was treated with methylprednisolone pulse, prednisone, and cyclophosphamide, but he died of respiratory failure.