Abstract： Objective To investigate the effect of different antidepressants (mirtazapine and fluoxetine) on food intake, body weight, tumor growth in a mouse model of pancreatic cancer. Methods A subcutaneous xenograft mouse model of human pancreatic cancer SW1990 was established. The tumor-bearing mice were randomly divided into saline solution control group, mirtazapine group, fluoxetine group, with 7 mice in each group. All mice were treated once daily with saline solution, mirtazapine (10mg·kg-1·d-1), fluoxetine (10mg· kg-1·d-1), orally by using metal garage feeding needles for 42 days. Tumor size, body weight, food intake were investigated. Results There was no significant difference in tumor size in the three groups. From the 2nd week, the food intake of mice in the mirtazapine group significantly increased compared with other two groups; the body weight of mice in the mirtazapine group at the 4th week was (16.00±1.41) g, which was higher than those in other two groups (P<0.05); from the 3rd week, the food intake of mice in the fluoxetine group significantly decreased compared with control group, and the body weight also decreased significantly from the 6th week (P<0.05) ; at the 6th week, the food intake of mice in the control, mirtazapine and fluoxetine groups were (3.54±0.13)g, (4.19±0.16)g and (3.34±0.13)g, and the body weight were (13.71±1.11)g, (14.86±1.68)g and (12.57±1.51)g, respectively. Conclusions Mirtazapine was better than fluoxetine in increasing food intake and alleviating body decreasing on a pancreatic cancer mouse model. However, there was no significant effect on the pancreatic tumor growth.