Abstract:[Background] Epichloë guerinii SC012 isolated from Melica transsilvanica, a plant only growing in the northern slope of the Tianshan Mountains in China, is a type of endophytic fungus of grasses. [Objective] To investigate the relationship between E. guerinii and the disease resistance of its host M. transsilvanica. [Methods] Dual-culture tests were conducted to assess the interactions between the endophytic fungus and four common plant pathogenic fungi. A pot experiment was performed to evaluate the resistance of M. transsilvanica with E. guerinii to pathogen invasion. [Results] In the dual-culture tests, E. guerinii isolated from M. transsilvanica exhibited inhibitory effects on Rhizoctonia solani, Alternaria tenuis, and Colletotrichum cereale, with the inhibition rates of 57.39%, 26.30%, and 20.92%, respectively. The fermentation broth of E. guerinii also inhibited the growth of the three pathogens, with the inhibition rates of 64.94%, 32.93%, and 15.61%, respectively. The endophytic fungus and its fermentation broth had no impact on the growth of Fusarium sp. The results of the pot experiment showed that E. guerinii reduced the disease indexes of M. transsilvanica exposed to the invasion of R. solani, A. tenuis, and C. cereale, with the relative protective effects of 36.61%, 16.01%, and 21.87%, respectively. Apart from reducing the incidence caused by R. solani, E. guerinii showed no significant effect on the incidence caused by other pathogens. M. transsilvanica plants with the endophytic fungus (E+) had higher polyphenol oxidase (PPO) and phenylalnine ammonialyase (PAL) activities than the plants without the endophytic fungus (E‒) (P<0.05), except that the PAL activity had no significant difference in the case of Fusarium sp. infection. [Conclusion] The endophytic fungus E. guerinii can enhance the resistance of M. transsilvanica to specific pathogens, while the resistance varies depending on the pathogens. The findings provide a basis for the use of endophytic fungi of grasses in the biocontrol and breeding of disease resistant crops.