Brassinosteroids (BRs) play an important role in the regulation of plant growth and development in response to environmental stresses. The effect of 24-epibrassinosteroid (EBR) (0 and 10(-7) M) on some physiological parameters of three safflower cultivars (Goldasht, Faraman and Sina) was investigated in three irrigation schedules (included; irrigation at 80 (I-1), 120 (I-2) and 160 mm (I-3) evaporation from class-A pan) in Ardabil province in 2015. The results showed that drought stress decreased the chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid content, activity of peroxidase (POD) and relative water content (RWC). Activities of superoxide dismutase (SOD), catalase (CAT), polyphenol oxidase (PPO), ascorbate peroxidase (APX) enzymes were increased in response to drought stress as well as EBR application. Application of EBR significantly declined the amounts of malondialdehyde (MDA), and electrolyte leakage by increasing antioxidant enzymes activity and carotenoid under drought stress. Also, 24-epibrassinosteroid increased the chlorophyll-a, chlorophyll-b, and total chlorophyll. Generally, we concluded that the application of 24-epibrassinosteroid can be a proper tool for increasing safflower yield under water deficit stress especially in Faraman cultivar.