Early blight disease caused by Alternaria solani fungus is one of the most important diseases attacking tomato especially in humid regions with high temperatures (24-29°C). Controlling the early blight disease using fungicides has become unfavorable in the last years due to their environmental and human health concerns. Biotic and abiotic induction of host plants defense mechanisms could be applied as an alternative management strategy against the disease. Nowadays, different Trichoderma species could be used as one of promising bio-control agents affecting development and disease incidence of Alternaria solani on tomato plants. In present study, the direct and indirect effects of different Trichoderma isolates application on Alternaria solani infection as well as on the gene expression levels of some related genes to defense mechanisms in tomato plants was investigated. Results indicated that Trichoderma species reduced either the mycelial growth or the disease incidence of Alternaria solani. Treating tomato roots with Trichoderma harzianum-T10 isolate affected the relative expression levels of eight different genes within tomato leaves. Three genes of them i.e., Les.21895, Les.19403 and Les.1097, which involved in auxin, ethylene and lignin pathway respectively, were up regulated while the other three genes i.e., Les.20348, Les.3129 and Les.9833, which related to pyruvate kinase pathways, were down regulated. In addition, treating tomato plants with Trichoderma harzianum T10 regulated the expression level of some Pr-protein genes i.e., Pr-1 and Pr-5. These findings suggested that induction of systemic defense mechanisms using the mutualistic Trichoderma isolates such as T10 is candidate to be among the mechanisms that can play a crucial role in controlling tomato early blight disease caused by Alternaria solani.