This work was conducted in the regional laboratory for food and feed, Agriculture Research Center, Giza, Egypt, in a closed recirculation water system for 12 weeks to determine the effect of replacing 0, 10, 20, 30 and 40% soybean meal and yellow corn in tilapia (Oreochromis niloticus) diets by Distillers Dried Grains (DDGS) with and without enzyme (Ameco Zyme 2x, 0.25g/kg). Therefore, nine isonitrogenous (30% CP) and isocaloric (3200 kcal GE/kg) experimental diets were formulated, D1, repsant the (control). In the other experimental diets, soybean meal and yellow corn mixture was replaced with DDGS at a rate of 10% (D2), 20% (D3), 30% (D4), 40% (D5), 10% DDGS+ Enzyme (D6), 20% DDGS+Enzyme (D7), 30% DDGS+ Enzyme (D8) and 40% DDGS+ Enzyme (D9). A total number of 405 tilapia fry (0.98 g±0.01) were randomly distributed into 27 tanks (60 liters each) at a stocking rate of 15 fry/tank. After 84 days from the experiment start no significant differences (P