This trial aimed to study the effect of using dried distillers grains with soluble (DDGS) at different levels as partial substitute for protein sources in rations of lactating Friesian cattle. Twenty five Friesian cows were chosen and used in feeding trial (which lasted 210 days) during year of 2011. Animals were divided into five similar groups, which received concentrate feed mixture containing DDGS at rate of 0, 11, 16, 21 and 27% to cover 0, 20, 30, 40 and 50% of the dietary protein content, respectively. In addition, berseem hay and wheat straw were offered. The percentages of feed offered from the concentrate feed mixture, berseem hay and wheat straw were 70, 20 and 10%, respectively, according to NRC (2001). Milk yields of experimental animals were determined and analyzed. Also, samples of rumen liquor and blood were collected and analysed. Feed and economical efficiencies were estimated. Additionally, five digestibility trials were carried out using three Friesian cows in each treatment to determine the digestion coefficients and nutritive values of different experimental rations using insoluble ash technique (AIA) as a natural marker. The results obtained were as follows: 1-The DM consumption increased with increasing dietary DDGS levels. In addition, digestibility was significantly (p<0.05) higher for all nutrients except EE. However, increasing DDGS levels in experimental rations from 11 to 16% or from 21 to 27% did not have significant effect on nutrient digestibility and nutritive values expressed as TDN (%) or DCP (%). 2-Actual milk and 4% fat corrected milk yields increased with increasing DDGS levels in the rations of lactating Friesian cows, while increasing DDGS levels from 11 to 16% or from 16 to 21% did not have significant increase in milk yield, but increasing DDGS levels from 21 to 27% tended to significant (P<0.05) higher in both actual milk and 4% FCM yields with rate of 5.86% and 4.75%, respectively. 3-Fat and protein percentages of milk and their yields were affected by adding DDGS in ration. However, % total solids (TS%) and solid not fat (SNF%) were not affected, while their yields showed significantly, (P<0.05) increase with increasing DDGS levels in rations. 4-Animals fed ration E (containing 27% DDGS) were the best group in feed utilization efficiency expressed as kg DM per kg milk (1.015 kg) or 4%FCM (1.043kg). 5-Feed cost per kg of both milk and 4% FCM decreased with increasing DDGS levels in ration of lactating Friesian cows. Animals fed the cheapest ration (Ration E, containing 27% DDGS) gave the highest net revenue and the best economic efficiency. The improvements in net revenue and economic efficiency were 48.59% and 32.22%, respectively. 6-Increasing DDGS levels up to 27% in the ration of lactating Friesian cows significantly (P<0.05) increased total nitrogen (TN), ammonia nitrogen (NH3-N), Etman, K. O. E. et al. 524 proteinnitrogen (PN) and VFA's concentrations in rumen liquor. Also, GOT and GPT concentrations in blood serum were significantly (P<0.05) higher, while differ...