One of the major problems facing poultry nutrition in Iran is large fluctuation in market price of protein resources. In order to reduce feeding costs, attempts have been made to use agricultural and industrial byproducts as feed ingredients. In line with this strategy, this study was conducted to evaluate the effects of enzyme supplementation of safflower meal-included diets on productive performance, egg quality characteristics and some blood parameters of laying hens. A total of 250 white leghorn hens Hy-Line, W-36 strain were divided in 50 cages (n=5). Based on a 5×2 factorial arrangement of treatments, ten isocaloric and isonitrogenous diets (ME =2750 Kcal/Kg and CP=14.61 g/Kg) including 5 levels of safflower meal (0.0, 25.0, 50.0, 75.0 and 100.0 g kg?1) with and without enzyme (Bergazym P®, 0.0 and 1.0 g kg?1) were assigned to hens in 5 cages (replicates). During the 10 weeks of experimental period, eggs were collected and weighed daily, and feed consumption was weekly recorded. After 48 and 55 days of experiment, birds were injected with 1 mL of 7% Sheep Red Blood Cells (SRBC) intramuscularly. At the end of experiment, the antibody titer against SRBC and differential circulating leukocyte count were measured for investigating of immune status. Data was analyzed based on completely randomized design using GLM procedure of SAS. Dietary inclusion of safflower meal and enzyme supplementation had no significant effect on egg quality traits. However, the performance was improved in the hens fed on safflower meal diets as well as enzyme-supplemented diets. Birds received dietary inclusion of safflower meal, have higher egg production, significantly (P 0.05). Dietary safflower meal inclusion improved egg production of hens in the levels of 2.5 and 5% (P 0.05) during weeks 7 till 8, however this parameter was not affected during the all experimental period (1-10). Hens fed safflower meal diets improved feed conversion ratio in the levels of 0.0, 2.5 and 5%, however the reverse trend was found in the levels of 7.5 and 10. Using safflower meal diets increased feed intake during the all experimental period slightly (P=0.095). Also, enzyme supplementation improved the feed conversion ratio during the experiment (P=0.11). Antibody titer against SRBC was not affected by treatment; however dissipation count of white blood cells was affected markedly (P 0.05). Therefore, our results indicated that safflower meal can be included in diets of laying hens up to 5% with no adverse effect on performance. Also, administration of cocktail commercial enzyme to the diets of laying hens would have beneficial effect on performance, especially in terms of egg production and feed conversion ratio. Key words : Safflower meal, enzyme, laying hens, performance, blood parameters.