Pot and field experiments were conducted at the Agric. Exp. Station of  El-MansouraUniv. During the winter season of (2008- 2009) and (2009-2010); respectively to investigate the possibility of partial or entirely substituting bio and organic fertilizers for cultivation of wheat plants instead of inorganic fertilizer. Forty treatments were arranged in split-split block design which were the simple possible combination between, two treatments of farmyard manure; with (FYM) and without it (0) were arranged as main plots. Four treatments of NPK fertilizers at rates of 0, 50, 75 and 100% from the recommended doses by the Ministry of Agriculture and land reclamation (MALR) for wheat plants were randomly located as sup-plots. Wheat seeds were inoculated with biofertilizers and devoted as sub-sub plots as five treatments including; Control, cerealin, phosphoren, K-mg and a mixture of them at rate of 1:1:1. The obtained results indicated that: Adding farmyard manure in both years of the experiment significantly increased the average values of N, P and K% in the leaves, straw and grains and their uptake by wheat plant than those obtained for the untreated plants. Increasing NPK- applied level from 50 to 75% and, furtherly to 100% RD significantly increased the aforementioned traits. The highest mean values for the previously mentioned traits were found to be associated with the addition of 100% RD-NPK. Inoculation of wheat seedlings with single or mixed biofertilizers was responsible for the statistically increase in the previously mentioned traits. Always, the mixed biofertilizers was pronounced and associated with the heighest mean values for all aforementioned traits. Co-inoculation of wheat seeds with (Cerealin), (Phosphoren) and (K-Mg) in single form or as a mixture in combination with the ra tes of NPK-applied in the presence and absence of FYM significantly resulted in high N and P contents in the leaves, straw and grains of wheat plant than those obtained for the untreated plants. In addition, the heighest mean values for the previously mentioned traits were connected with the treatment of 75 % RD + FYM + Mix during both season of the experimentation. On the contrary of this trend, the differences between the values of K% in the grains of wheat plant did not reach the level of significance during both seasons of the experiment. However, at any fertilization treatment the use efficiency of N, P and K appeared higher for the plants treated with N, P and K fertilizers at rate of 50% RD in combination with inoculation wheat seeds with the mixture of biofertilizers in the presence of FYM at  rate of 20 m³/fed. Thus, it could be recommended that inoculation of wheat seeds with the mixture of biofertilizers combined with N, P and K fertilization at the rates of 57, 11 and 14 kg.fed^-1 respectively, and farmyard manure ; 20m³.fed^-1 are considered as the most suitable treatment for realizing the highest economic yield for wheat.