Background Triamcinolone acetonide (TA) is often used in the treatment of uveitis and fundus disease,but whether it has toxic effect to normal tissue around eyes is unclear.Objective The aim of this study was to explore the adverse and toxic effects of TA on the periorbitally normal tissue following the periocular injection.Methods Twenty-seven New Zealand albino rabbits were randomly divided into experimental group,normal saline solution group and blank control group.TA was periocularly injected twice (20 mg for each) at 1-month interval in the rabbits of the experimental group,and 0.5 ml normal saline solution was used in the same way in the rabbits of the normal saline solution group.Not any drug was used in the blank group.The rabbits were sacrificed 1 month and 2 months,3 months after the secondary injection.For the preparation of the specimens of extraocular muscles,peribulbus adipose tissue,lacrimal gland and optic nerve.Hematoxylin and eosin staining of the specimens was performed to examine the the pathological change under the optical microscope,and the ultrastructural of peribulbus tissues was observed under the transmission electron microscope.Results No statistically significant change was found in IOP among various time points and groups (Fgroup =0.952,P =0.881 ; Ftime =7.297,P =0.411).The hyphological structures and ultrastructure of extraocular muscles,peribulbus adipose tissue,lacrimal gland and optic nerve were normal in the rabbits of the normal saline solution group and the blank control group.However,the optical microscopy showed varying degrees of atrophy or dissolving in the extraocular muscle fibers,the increase of glandular epithelial cells and enlargement of nuclei in the lacrimal gland as well as visible disorder arrangement of nerve fibers,vacuoles degeneration and the decrease of glial cells in optial nerve tissue in the rabbits of the experimental group from 1 month though 3 months after the secondary injection.Under the transmission electron microscope,the muscle stripes,bright band and dark band were incompletely disappeared,and expansionary sarcoplasmic reticulum and oval nucleus at the inferior to sarolemma were seen in the extraocular muscles.In addition,swelling lacrimal gland epithelial cells,thickening nuclear membrane and more organelles were exhibited in the lacrimal gland.In the optic never tissue,uneven myelin,space between axons and myelin,lamellar separation and degeneration also were revealed in the rabbits of the experimental group after injection of TA.Peribulbus adipose tissue was near normal both by optical microscope and transmission electron microscope in the experimental group.Conclusions The periocular injection of TA dose not elevated the IOP.However,it will result in the histogical and ultrastructural damages of extraocular muscles,lacrimal gland and optic nerve.