Objective To investigate the role of somatostatin and related signal transduction molecules in the process of spleen deficiency syndrome combined with gastric ulcer. Methods Seventy adult male and female Wistar rats were selected to set up an animal model of spleen deficiency syndrome combined with gastric ulcer. Then immunohistochemistry, reverse-transcript PCR, Western blotting and hematoxylin-eosin staining were used to detect the changes of somatostatin, somatostatin receptor 2 mRNA, excellular signal_regulated kinase 2(ERK2) and histological structure of gastric mucosa respectively. Results In the gastric mucosa of spleen deficiency syndrome combined with gastric ulcer, the content of somatostatin increased and the mRNA of somatostatin receptor 2 increased, while the content of ERK2 decreased. Conclusion Somatostatin signal transduction pathway may probably play an important role in the onset of spleen deficiency combined with gastric ulcer.