In order to evaluate response of Pishgam wheat cultivar to manure and biological substrate, a factorial experiment based on RBCD (randomized complot block design with 3 replications was done. The first factor was manure with three levels including 0, 7.5 and 15 ton per hectare, and second factor was biological substrata consumption including 0, 3 and 5 times. Traits under study were plant height, ear length, number of ear per square meter, number and weight of kernel in ear, 1000 kernel weight, biological and economical yield and also harvest index. Analysis of variance showed that manure had significant effect on all traits except plant height and ear length. By increasing of manure consumption from 7.5 to 15, yield component were increased. Effect of biological substrate on plant height, kernel weight in ear and 1000-kernel weight, was significant (P≤0.01). Maximum economical yield was obtained from 3 times biological substrate consumption and 15 tons manure with 26.6% increase compare to check treat. Highest biological yield was gained from 7.5 tons manure and 3 times biological substrate treatment and also the highest harvest index was earn from 7.5 tons manure and 5 times biological substrate treatment with 24.6% and 5% increasing respectively compare to check. It seems biological substrate effects in fertile soils is lower than non-fertile soils.