This greenhouse experiment, consisted of a completely randomized factorial design, was conducted to investigate the changes in antioxidant enzyme activities of lettuce plants cv. Syahoo inoculated with Piriformospora indica fungus under different levels of zinc (0, 2.5, 5 and 10 mg l^-1) in the research laboratory of Maragheh university in spring 2016. Fungal treatment was added at two leaf stage of seedling on the lettuce roots in the sandy substrate. The plant samples, at 35 days after sowing, were measured for dry and fresh weights of shoot, total soluble protein, malondialdehyde (MDA) concentration and activities of antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (GPOX), and catalase (CAT). The results revealed that the effect of P. indica and zinc application on dry and fresh weights of shoot, total soluble protein and activity of SOD were significant at P≤0.01. The main effect of zinc on MDA concentration, activity of GPOX and CAT was significant at P≤0.01. Highest amount of dry and fresh weights and total soluble protein, and maximum activity of SOD were obtained in presence of P. indica under 10 mg L^-1 Zn. Maximum activity of CAT, GPOX, and MDA concentration were observed in treatments without zinc application. Results from our research showed that inoculation by P. indica and zinc application (especially at 10 mg L^-1) have an important role in enhancing the growth parameters and modulating the activities of antioxidant enzymes in lettuce.