The aim of this study is to investigate the serum levels and clinical significance of nerve grow factor (NGF) and brain-derived neurotrophic factor (BDNF) in Sjogren's syndrome (SS) with interstitial lung disease (ILD). Fifty two untreated patients with SS were enrolled in the study. Of them, 25 patients only displayed salivary glands damage and/or lacrimal gland injury (simple SS group). The other 27 patients were lacrimal and/or salivary gland involvement as well as being concomitant only with intestinal lung disease (ILD group). Twenty-five serum samples from healthy volunteers were examined as controls. We measure serum NGF and BDNF levels by ELISA and correlate them with clinical data. Serum NGF levels were significantly higher in ILD patients (372 ± 129 pg/ml) and simple SS patients (293 ± 72 pg/ml) when compared with healthy controls (187 ± 47 pg/ml) (both p < 0.01). Significant difference were also found between the two patient groups (p < 0.01). In contrast, BDNF were significantly decreased in ILD patients (1,005 ± 143 pg/ml) when compared with either simple SS patients (1,204 ± 176 pg/ml, p < 0.01) or healthy controls (1,217 ± 155 pg/ml, p < 0.01). Correlation analysis showed NGF levels in ILD patient were positively correlated with serum levels of C-reactive protein and IgG (both p < 0.05). The abnormal NGF and BDNF in sera may be a potential character of ILD secondary to pSS.