Nowadays, there is a call for the reduction of the environmental pollution resulted from over application of chemical fertilizers. Therefore, study has been done to investigate the possibility and efficiency of using bio-fertilizers. Two field experiments were carried out during the two successive summer growing seasons of 2016 and 2017 at El-Mattana, Agriculture Research Station (latitude of 25 ^o 17′ N and longitude 32 ^o 33′ E), Luxor Governorate, Egypt to evaluate the influence of two sesame varieties (Sohag 1 and Shandaweel-3) and eight  different fertilizers treatments: 0, 50, 75, 100% of recommended nitrogen, phosphorus and potassium (NPK), bio-fertilizers, 50% NPK + bio, 75% NPK+ bio and 100% NPK + bio on sesame  yield. Treatments were carried out as Split Plot Design with three replicates, varieties in the main plots and fertilization treatments in the sub plots. The results could be summarized as follows: Shandaweel-3 variety surpassed Sohag-1 variety in all studied characters.  Except umber of capsules/plants, length of fruiting area, harvest index, oil yield, K uptake in seed and NK uptake in straw. The addition of 100% mineral recommended dose of NPK + Bio fertilizer resulted in a significant increment in sesame yield and its components in both seasons. The highest oil yield and content of N and P were obtained from Shandaweel-3 with fertilization at 75% NPK+ Bio-fertilization treatment. The results showed the importance of using bio-fertilizers to protect the soil and the environment from harmful chemical pollution.
The highest values of protein %; NP-uptakes in straw yield were obtained with 75% mineral NPK+ Bio-fertilization in both seasons, and also gave high values of seed and straw yields (kg/fed) and harvest index %. The highest content of N and P (as %) were obtained from Shandaweel-3 with fertilization at 75% NPK+ Bio-fertilization treatment, which also gave the highest N and P uptake by same variety. The results showed the importance of using bio-fertilizers to protect the soil and the environment from harmful chemical pollution.