Objective To investigate the clinical efficacy and safety of intraductal meibomian gland probing in the treatment of patients with meibomian gland dysfunction （MGD）． Methods In a prospective randomized block design， 111 consecutive patients （111 eyes ） with MGD were divided into 3 groups． All subjects were age- and sex-matched among the 3 groups. The eye selected for the study in each subject was chosen on the basis of the most obvious symptoms. There were 37 eyes in each group． The conventional treatment group was treated only with antibiotic eye drops combined with topical steroids+artificial tears+local physical therapy； MGD patients in the intraductal probing group underwent intraductal probing with steel probes （Rhein Medical， Inc. USA） and 6～9 meibomian glands were probed in each eye； and the third group underwent intraductal probing combined with a drug（0.5% tobramycin dexamethasone eye drops） injected into the intraductal meibomian gland during the probing procedure. All subjects underwent sequential examinations before and after treatment as follows： evaluation of ocular surface disease symptoms using the ocular surface disease index （OSDI）； tear film break-up time （BUT）； corneal fluorescein staining （CFS）； Schirmer I test （SIT）， and lid margin and ocular surface examination by slit lamp． The parameters among the 3 groups were investigated and compared before treatment and 1 month after treatment． Confocal microscope was performed to detect the safety of the intraductal meibomian gland probing by observing both the morphology and density of meibomian gland （MG） acinar units. The data among the three groups were randomly compared by a two-way ANOVA and q test （Newman-Keuls）； a paired t test was used to analyze the parameters in each group before treatment and 1 month after treatment. Results ①Before treatment， there were no statistical differences among the three groups in OSDI， BUT， CFS， SIT， or lid margin scores （P＞0.05）. ②There were statistical differences among the three groups 1 month after treatment（F=4.68， 4.17， 3.98， 3.67， 4.12， P＜0.05）. The changes in every parameter in the conventional treatment group were significantly lower than for those in the intraductal probing group （P＜0.05） and in the intraductal probing group that received drug injections （P＜0.05）. Improvement was better in the intraductal probing group that received injections compared to the intraductal probing group but no statistically significant differences were seen in the parameters. ? ③1 month after treatment： except for the conventional treatment group， significant differences were noted in the data of OSDI， BUT， CFS， Schirmer I test， and lid margin scores in the intraductal probing group （t=2.543， 2.343， 2.456， 2.132， 2.237， respectively， P＜0.05） and in the intraductal probing with drug injection group （t=2.713， 2.443， 2.496， 2.143， 2.249， respectively， P＜0.05）. ④The MG acinar cells can be clearly observed with confocal microscope. MG acinar cells showed that different forms were due to the location in different optical sections. The outer sections of MG acinar cells were tire-like， accompanied by bright reflective and gray cell cavities with highly reflective dot secretion. MGs were distributed in group-like aggregations and arranged irregularly. There were no degenerative changes in the morphology of MG acinar units as well as MG scars 1 month after probing. Conclusion Intraductal meibomian gland probing seems to provide rapid and lasting symptom relief and significant improvement in symptoms and signs of MGD in patients. Intraductal meibomian gland probing is a safe， effective technique for MGD．