Abstract: Different sizes of Onchidium strumas were divided into three groups, which were below 8 g, 8-18 g and upward of 18 g group. The histological structure and the number of 5-HT and substance P positive cells in stomachcaeca of different sizes of Onchidium strumas were observed by histology and immunohistochemical methods. The results showed that histologically, two types of villis, spindly and non-spindly, were found in stomach caeca of Onchidium strumas. The percentage of non-spindly villis was reduced with body weight of Onchidium strumas increasing. The much more spindly villis were distributed in upward of 18 g Onchidium strumas. The percentage of spindly villis (66%) was about two-fold more than non-spindly villis (34%) in upward of 18 g group. Numerous 5-HT cells and substance P were detected in the epithelial mucosa of Onchidium strumas stomach caeca villis, especially in non-spindly villis. The percentage of positive non-spindly villis of both 5-HT and substance P were 10 times more than that of spindly villis. The number of positive cells of both 5-HT and substance P in stomach caeca were significantly increased in a weight-dependent manner, from below 8 g to unward of 18 g group. The amount of 5-HT in upward of 18 g group (112.82 ind/cm²) was about 3-fold more than that inbelow 8 g （34.8 ind/cm²）, meanwhile, the amount of substance P in upward of 18 g group（177.48 ind/cm²） was about 3.5 fold more of that in below 8 g （51.08 ind/cm²）. The amount of substance P was higher than that of 5-HT in three groups, and increased with weight.