AIM:To investigate the immunomodulatory mechanism of FK506 on the local Th1/Th2 balance in mice model of experimental allergic conjunctivitis. METHODS: Experimental allergic conjunctivitis model was established through peritoneal injection of phosphate buffered saline(PBS) in SPF level Balb/c mice. In all, 80 mice were equally divided into 4 groups: model group, Dexamethasone (DM) group, FK506 group, and normal group. Fifteen days after the introduction of experimental allergic conjunctivitis, DM group and FK506 group mice were treated by 1g/L Dexamson eyedrops and FK506 eyedrops respectively, four times a day. Samples from one eye of the mice were used for histological study, while samples from the other eye were used for detection of interleukins. RESULTS: The strong positive rate (SPR) of eosinophilic granulocyte and CD4+ lymphocyte were both 85% in model group. SPR of eosinophilic granulocyte was 50％,and CD4+ lymphocyte was 40% in DM group. SPR of eosinophilic granulocyte was 30％,and CD4+ lymphocyte was 40% in FK506 group. The level of IL-4,IL-6,IL-10,IL-2,IL-12,IFN-γ were significantly higher in model group compared with normal group （F＝11.278，P＝0.000），while IL-4/IFN-γ,IL-6/IFN-γ, IL-10/IFN-γ were also significantly higher than normal group （F＝8.965，P＝0.000）. The level of IL-4,IL-6, IL-10 was significantly lower in DM group compared with model group（F=13.972, P=0.000）, the level of IL-12 significantly higher（F=6.408, P=0.002）, while the level of IL-2 and IFN-γ showed no significant change（F=1.824, P=0.306）. The level of IL-4,IL-6,IL-10 was significantly decreased in FK506 group compared with model group（F=10.582, P=0.000）, the level of IL-12 was significantly increased（F=9.643, P=0.001），while the level of IL-2 and IFN-γ showed no significant change（F=2.529, P=0.407）. The level of IL-4,IL-6,IL-10 was significantly reduced in FK506 group compared with DM group（F=11281, P=0.000）, the level of IL-12 was significantly increased（F=8.634, P=0.003），while the level of IL-2 and IFN-γ showed no significant change（F=0.756, P=0.305）. CONCLUSION: The suppressive effect of FK506 on eosinophilic granulocyte and CD4+ lymphocyte was evidently stronger than that of Dexamethasone. FK506 can shift the local Th1/Th2 balance of experimental allergic conjunctivitis toward Th2 direction with better effect than that of Dexamethasone.