Abstract: Introduction: Cytotoxic drugs are all effective in the treatment of ocular lesions of Behcet’s disease (BD). However, with all methods there are some patients that their eye lesions will progress despite the treatment. This study was designed to find whether a combination therapy with 2 of these drugs could have better effect in reducing the rate of non-responders. Materials & Methods: Twenty eight patients diagnosed as BD (according to the Iran and to the Japan criteria) with posterior uveitis (PU) and/or retinal vasculitis (RV) were selected. They all received low dose pulse cyclophosphamide (LDP) as 0.5 g/m2/month by intravenous infusion, Methotrexate (MTX) as 7.5 mg/week orally in 3 divided doses, and Prednisolone 0.5 mg/kg/day orally. A Disease Activity Index (DAI), based on the inflammatory state of each section of each eye, a visual acuity (VA) measure for each eye, and a Total Adjusted DAI for each patient was calculated. Improvement and stabilization of the lesions were classified as good result. The comparison of these data before and after the treatment was made by the student paired t test. Results: The mean follow up time was 8 months. We had good result for the anterior uveitis (AU) in 89% of the eyes; the mean DAI decreased from 2.8 to 1.5 (p=0.09). In PU the good result was seen in 84% of the eyes; the mean DAI decreased from 2 to 1.3 (p<0.006). RV showed good result in 70% of the eyes; the mean DAI decreased from 4.2 to 2.8 (p<0.006). VA improved in 70% of the eyes; the mean VA increased from 3.2 on 10 to 3.9 on 10 by the Snellen chart (p=0.09). The total adjusted DAI improved in 79% of the patients. The mean total adjusted DAI decreased from 53.9 to 40.5 (p<0.003). Adverse effects were seen in 8 patients (29%). They were mainly mild and reversible increase in liver enzymes (seen in 5 patients), which led to MTX discontinuation only in I one case. We compared these results with patients who received LDP or MTX alone, after the same I mean follow up time. In 153 patients receiving MTX the good results were as follow: 86% in AU, 87% in PU, 83% in RV, 75% in VA and 75% for the total adjusted DAI. The good results in 70 patients receiving LDP were: 88% in AU, 87% in PU, 75% in RV, 76% in VA and 74% for the total adjusted DAI. There was no statistically significant difference between them. Conclusion: Combination therapy with LDP and MTX in ocular lesions of BD has no superiority to single therapy with the same drugs, at least in short term use. As the rate of side effects did not increase with their combination, long-term use is permitted and better results may be achieved in long-term follow up.