Lung cancer often develops in patients with interstitial pneumonia (IP). Chemotherapy for lung cancer patients who have IP is difficult because of the increased likelihood of acute exacerbations (AE) of IP or chemotherapy-induced pneumonitis. Furthermore, little is known regarding chemotherapy for previously treated patients having lung cancer associated with IP. We retrospectively evaluated the safety and efficacy of pemetrexed monotherapy for previously treated patients with non-small cell lung cancer (NSCLC) and IP. We enrolled 50 NSCLC patients and evaluated 5 patients with IP from among them. The median age was 68 years. The treatment line of pemetrexed included second line in two patients, and third line or more in three. The response rate was 0%, and the disease control rate (complete response+partial response+stable disease) was 60%. Pemetrexed-induced pneumonitis occurred in two patients (40%). The two patients who developed pneumonitis had mild IP. Therefore special attention should be paid when using pemetrexed for previously treated patients with lung cancer and IP, even for mild stage IP.