Safflower having oil with high unsaturated fatty acids is a very valuable plant. However the sensitivity of safflower to some pests as safflower fly (Acanthiophilus helianthi), particularly in drought stress conditions has limited its production. In order to evaluate the effect of drought stress on population density and damage of important safflower pests, especially safflower fly, an experiment was conducted in the field using 5 irrigation treatments including 50, 70, 90, 110 and 130 mm evaporation from class A pan in a randomized complete block design with three replications. The local safflower variety used in this study was Isfahan land variety, Kooseh. In each irrigation regime, the half of one plot was locally sprayed by Chlorpyrifos in 2ml per liter of water to be compared with non-sprayed part. During 8 weeks of sampling, population of aphids, Uroleucon carthami, leafhopper, Empoasca decipiens and safflower fly, A. helianthi and also percentage of damaged heads by safflower fly were measured. The results showed that in non-sprayed conditions, the highest safflower fly (2.38 flies per net) and aphid population (165.57 aphids per plant) was observed at 130 mm evaporation regime. Drought stress also decreased (30.23 %) safflower seed yield. Severe drought stress together with non-spaying may increase safflower pests population particularly safflower fly and reduce seed yield. However low level of drought stress (70 mm evaporation from class A pan) may decrease relative number of insects and save irrigation water. Drought stress also decrease the population of leafhopper. In this study, 70 mm evaporation regime was the optimum irrigation treatment regarding lower aphid and fly damage (15.86% damaged heads in non-sprayed condition) and higher safflower seed yield (1687.5 kg/ha in sprayed condition).