Objective To investigate the effect of Citalopram on tear film function and corneal epithelium in mice. Methods A total of 36 BABL/c male mice were randomly divided into group A, group B and group C. Mice in group A received no treatments. Mice in group B received saline (10 ml/kg) via intraperitoneal injection. Mice in group C were intraperitoneally injected with Citalopram (10 mg/kg) on daily basis. Schirmer I test (SIT) and the break-up time (BUT) were carried out on day 1, 4 and 7 post insults. On the 7th day, corneal fluorescein staining (FL) was carried out, and histological analysis of eyeballs of mice were evaluated by scanning electron microscope (SEM) and HE staining. Results SIT, BUT and FL were significantly different on day 1, 4, and 7 in three groups (F = 9.749, 10.427 and 6.752, P = 0.008, 0.019 and 0.032, respectively). SIT, BUT and FL were statistically different among group A, group B and group C (F = 11.234, 14.842 and 5.337, P = 0.002, 0.012 and 0.029, respectively). Seven days after the intervention, numbers of epithelial cavitation cells in group A, group B and group C were obviously different (F = 7.749, P = 0.013). Mice in group C experienced villi decrease without significant difference among groups (F = 0.917, P = 0.092). Conclusions Citalopram damages the function of tear film while exerts no effect on corneal epithelial tissue in mice model.