45 samples were collected from various sources (soil, degraded wood and mushroom compost) from three cities (Damascus, Homs and Lattakia). 18 Trichoderma isolates were isolated and identified by microscope. These isolates were screened using CMC medium with Congo red dy to identify their ability to produce cellulase complex. The amount of enzyme production was determined depending on the radius of clear zone around the colony. Results showed that the most productive isolate was Tr with radius 7 ± 0.2 cm followed by Tg and Ti. Optimization of cellulase production was performed using response surface methodology (RSM). The optimal parameters were: temperature 29.5 ˚C, pH = 6، incubation time 4 days, aeration speed 175 rpm and wheat straw concentration 3%. All studied parameters had significant effect on cellulase enzyme activity.