This study was performed to estimate the effect of protein, forzymedry© enzyme (cellulase, xylanase, B-glucanase, pectinase and galactosidase) and their interaction on the growth performance, body composition, some blood metabolites and histological statement of Nile tilapia, Oreochromis niloticus fry. A factorial trial (2 x4) two levels of dietary protein 20 and 25% (D20& D25) with four levels of forzymedry enzyem as feed additives (0, 25, 50 and 75 mg/kg diet). Results showed that, growth rate was not significantly differed by dietary protein but protein efficiency ratio (PER) was increased significantly (P<0.05) by increasing protein level.  Increased dietary forzymedry enzyme level resulted in enhancing feed efficiency ratio, protein efficiency ratio, and survival rate significantly (P<0.05). The interacted effect influenced significantly (P<0.05) on all parameters of growth performance except for feed intake. And dietary 20% CP with adding 75mg/kg of enzyme had the best growth patamteres. The higher whole body protein of tested fish was obtained by 20% CP diet supplemented with  adding 25 and 50 mg/ kg of Forzymedry© enzyme  compared to other experimental diets. There were slightly differences among different interaction patterns of supplemental protein and enzyme for blood parameters as total protein, albumin, globulin and glucose. Also, there were no hazards effects on the histology statement with protein levels and/or forzymedry© enzyme. So, it can be use Forzymedry© enzyme with dietary lower total protein levels of 20 and 25% of Nile tilapia, Oreochromis niloticus fry.