Improved yield and oil of safflower is one of the main objectives of breeding in safflower, but uses of safflower in the drug discovery, natural colors and spice industries are also prominent. Therefore improving the quality and quantity of related traits is necessary. In order to investigate the variation of p0henolic compounds in leaves and seeds of safflower in two sowing dates, 19 genotypes including F5 populations (9 genotypes) derived from inter-specific crosses of cultivated and wild safflower ( Carthamus oxyacanthus ), cultivated genotypes (6 genotypes) and wild safflower genotypes (4 genotypes) were evaluated. Genotypes were planted according to a randomized complete block design with three replications in two seasons of spring and summer at research field of Isfahan University of Technology. Agronomic traits, flavonoid content of seed coats and leaves and also the relationship between flavonoid content and agronomic traits and resistance to safflower fly ( Acanthiophilus helianthi ) were studied. Analysis of variance showed that there was significant variation for all traits. The effect of planting dates was also significant on all traits except for head diameter, leaf phenolic (flavonoid) content and the ratio of colored seeds in seed mass. The average of traits associated with vegetative growth was significantly higher in spring planting date than summer planting date. Wild genotype had more number of heads per plant compared with cultivated genotypes, but the number of seeds per head was significantly less in wild genotypes. Averagely, the percent of seed oil in all three categories of genotypes was higher in summer planting date than spring planting date. The frequency of safflower fly on genotypes was also significantly different in two planting dates. The genotypes derived from inter-specific crosses with black seed coat color had lower number of flies compared with those which had white seed coat color indicating that seed coat color is possibly effective on resistance to safflower fly. The results also showed that black seed coat color was correlated with higher phenolic (flavonoids) compounds. Cluster analysis grouped genotypes in four clusters and F5 genotypes with black seed coat color were separated from those with white seed coat color. Planting date significantly affect flavonoid content of seeds but leaf flavonoid content was not affected. The highest value of seed phenolic compounds was observed in seeds of cross 3 genotypes and the lowest one was for Arak 2811 cultivar. In the path analysis, the number of seeds per head significantly affected seed yield and head diameter indirectly affected seed yield through the number of seeds per head. Seed coat color and seed coat flavonoids had the most direct effects on Safflower fly frequency than flavonoid compounds of leaves. Seed phenolic compounds are also effective against safflower fly frequency indirectly through the seed coat color. It seems that seed coat color could be used for breeding resistant safflower genotype to safflower fly. Key word: safflower, leaf flavonoid compounds, seed flavonoid compounds, Seed coat color, Safflower fly