In this study, the effect of cyclosporin A (CsA) eye drop on keratoconjunctivitis Sicca (KCS) and its mechanism were studied. The KCS models were established by injecting Pertussis vaccine, complete freunds adjuvant (CFA) and antigen of conjunctiva from isotype mice. Then the KCS models were treated with cyclosporin A eye drop. Changes in breaking-up time (BUT), lacrimal secretion in 30 min and diversion in 24 h were measured. The percentage of beaker cells, the lymphocytic infiltration in conjunctiva were observed. The expression levels of Aquaporin-3(AQP3) in conjunctiva epithelial cells, beaker cells and accessory lacrimal gland were immunohistochemically detected. The results showed that there were significant differences in BUT, the percentage of beaker cells, lacrimal secretion in 30 min, the lymphocytic infiltration and the expression of AQP3 between the experimental group and an control group. It was concludedthat CsA eye drop exerts marked therapeutic effect on KCS by inhibiting T lymph cells, increasing the goblet cells and AQP3 expression in conjunctiva.