Introduction of physiological indices in relation to safflower drought tolerance has important role in selection of tolerant varieties. To study the effect of drought stress on some physiological characteristics of spring safflower, a field experiment was carried out in 2010 as a split-plot based on randomized complete block design with three replications at Research Farm Faculty of Agriculture of Yasouj University. Main factor included of irrigation after 70, 140 and 210 mm evaporation from class A evaporation basin and sub-factor included of four spring safflower varieties (Esfahan 14, Local variety of Esfahan, Goldasht and Sina 411). Results showed that interaction of varieties and drought stress and simple effect of experimental treatments was not statistically significant for chlorophyll fluorescence. Interaction of varieties and stress was statistically significant for relative water content, leaf proline content, leaf soluble sugar content. Maximum leaf relative water content in irrigation after 70 (83.83 percent), 140 (82.62 percent) and 210 (83.22 percent) mm evaporation was belonged to Goldasht. Maximum proline content (167.87 µmol g^-1 leaf fresh weight) in irrigation after 140 mm evaporation was belonged to Esfahan 14. Maximum leaf soluble sugar content in irrigation after 70 (632.81 mg g^-1 leaf fresh weight), 140 (677.56 mg g^-1 leaf fresh weight) and 210 (678.71 mg g^-1 leaf fresh weight) mm evaporation was belonged to Sina 411. We can say low level of water result in increase in proline amount in Esfahan 14 and increase in soluble sugar content in Sina 411.