In the present study, the effect of the intraperitoneal injection of Carthamus tinctorius extract on non-specific immune system and some serological of Oncorhynchus mykiss has been investigated. To this end, the fish with average weight of 100±10 gr were intraperitoneally injected by different levels of safflower extract. In this regard, a negative control group (no injection), a positive control group (injection with 0.2 ml physiologic serum) and three treatment groups received injections of C. tinctorius extract with the concentration of 50, 100 and 200 (mg/kg weight in the volume of 0.2 ml) respectively. Blood sampling were taken On the third, seventh and tenth days after injection, and total serum protein, total immunoglobulin, lysozyme activity, complement and blood glucose levels determined. The results showed that safflower extract injection led to a significant decrease in the number of white blood cells on the third, seventh and tenth days after injection (sig< 0/05). Moreover, blood glucose, lysozyme activity, total immunoglobulin and total protein levels significantly decreased. There was no significant change in complement activity among all groups. Considering this results, the use of safflower extract in rainbow trout can reduce and non-specific immune system activities.