Background: The presentation of acute eosinophilic pneumonia (AEP) closely resembles that of acute lung injury (ALI)/ARDS, including its idiopathic form, acute interstitial pneumonia (AIP). AEP usually lacks peripheral eosinophilia at the acute phase; therefore, the establishment of serum biomarkers for AEP would be clinically useful. Methods: We measured die levels of thymus- and activation-regulated chemokine (TARC)/CCL17, eotwdn/CCL11, KL-6, and surfactant protein-D (SP-D) in serum for patients with acute parenchymal lung diseases including AEP (n = 17), AIP (n = 13), pneumonia-associated ALI/ARDS (n = 12), and alveolar hemorrhage (n = 7). To evaluate diagnostic ability, each marker was estimated by measuring the area under the receiver operating characteristic curve (AUC). Results: Serum TARC/CCL17 levels of AEP patients were much higher than those of patients in other disease groups. More importantly, high circulating TARC/CCL17 levels were observed in AEP even at acute phase when peripheral eosinophilia. was absent. TARC/CCL17 showed the largest AUC, and the TARC/CCL17 levels with cutoff points from 6,259 to 7,039 pg/mL discriminated AEP from other syndromes with sensitivity and specificity of 100%. The KL-6 level was low in most patients,with AEP, and the sensitivity was 81.6% in cutoff with 100% specificity. The AUC for eotaxin/CCL11 and SP-D was small, with values of 0.73 (95% confidence, interval [CI], 0.60 to 0.86) and 0.53 (95% CI, 0.31 to 0.64), respectively. Conclusions: This study indicates that the measurement of circulating TARC/CCL17 and KL-6 is useful for discriminating AEP from other causes of ALI.